Bio

Academic Appointments


Administrative Appointments


  • Chairman, University panel on Radiation safety (2003 - 2010)

Professional Education


  • Licenciaat, KUL, Medical sciences (1978)
  • MD, Katholieke Universiteit Leuven, Medicine (1967)
  • PhD, UC Berkeley, Medical Physics (1972)

Research & Scholarship

Current Research and Scholarly Interests


Radio-immunotherapy.
Medical Imaging Processing.
Quantification for diagnosis
Clinical validations

Clinical Trials


  • S0016 Combination Chemotherapy With Monoclonal Antibody Therapy in Treating Patients With Newly Diagnosed Non-Hodgkin's Lymphoma Not Recruiting

    RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies can locate tumor cells and either kill them or deliver radioactive tumor-killing substances to them without harming normal cells. It is not yet known which monoclonal antibody plus combination chemotherapy regimen is more effective in treating non-Hodgkin's lymphoma. PURPOSE: This randomized phase III trial is comparing 2 different monoclonal antibodies given together with combination chemotherapy to see how well they work in treating patients with newly-diagnosed non-Hodgkin's lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lauren Pernicka, (650) 721 - 6977.

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  • Rituximab and Combination Chemotherapy in Treating Patients With Stage II, Stage III, or Stage IV Diffuse Large B-Cell Non-Hodgkin's Lymphoma Not Recruiting

    RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with combination chemotherapy may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy works in treating patients with stage II, stage III, or stage IV diffuse large B-cell non-Hodgkin's lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lauren Pernicka, (650) 721 - 6977.

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  • Assessing the Suitability of an Imaging Probe for Use in Clinical Cell and Gene Therapy Trials in Cancer and Rheumatoid Arthritis Not Recruiting

    The purpose of this study is to determine whether [18F]FHBG is suitable for use as an imaging probe in cancer or rheumatoid arthritis patients enrolled in cell or gene therapy trials. In this phase 1 study we will assess the safety and biodistribution of [18F]FHBG in patients.

    Stanford is currently not accepting patients for this trial. For more information, please contact Shahriar Shah Yaghoubi, Ph.D, 650-725-6070.

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  • Scintigraphic Assessment of I- Transport in Metastatic Breast Cancer and Evaluation of I31I Ablative Therapy: (Part I) Radioiodide Imaging Study Not Recruiting

    The purpose of this study is to examine breast cancers that express the protein (NIS) that may be found in malignant breast tissues and to evaluate proteins found in blood and their relationship to NIS, to test whether iodide can be concentrated by breast cells to possibly treat some breast cancers with radioactive iodine, and to calculate the amount of radioactive iodine entering breast cancer cells, how long your cancer retains the agent as well as how much is taken up by other organs, particularly the thyroid gland.

    Stanford is currently not accepting patients for this trial. For more information, please contact Marilyn Florero, (650) 724 - 1953.

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  • Study of Bexxar Combined With External Beam Radiation Therapy for Patients With Relapsed, Bulky Non-Hodgkin's Lymphoma Not Recruiting

    We hope to learn whether I-131 tositumomab combined with external beam radiation therapy is an effective means of treating relapsed, bulky non-Hodgkin's lymphoma. The purpose of the study is to determine the overall response rate with responses described as: Site-dependent and overall CR and functional CR (CR of CRu(Complete Response Unconfirmed)/PR with PET negativity), or PR rates.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lucy Schoen, (650) 725 - 1718.

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  • 90Y-IBRITUMOMAB Tiuxetan and AHCI With HD Chemotherapy and Autologous Transplantation for Relapsed or Resistant NHL Not Recruiting

    To test a new way to approach hematopoietic stem cell transplantation for Relapsed or Resistant Non-Hodgkin's Lymphoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact BMT Referrals, (650) 723 - 0822.

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  • Rituximab, Combination Chemotherapy, and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Stage I or Stage II Non-Hodgkin's Lymphoma Not Recruiting

    This phase II trial is studying how well giving rituximab together with combination chemotherapy and yttrium Y 90 ibritumomab tiuxetan works in treating patients with stage I or stage II lymphoma. Drugs used in chemotherapy, such as prednisone, cyclophosphamide, doxorubicin, and vincristine, work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab and yttrium Y 90 ibritumomab tiuxetan can locate cancer cells and either kill them or deliver radioactive cancer-killing substances to them without harming normal cells. Combining a monoclonal antibody with combination chemotherapy and a radiolabeled monoclonal antibody may kill more cancer cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office, (650) 498 - 7061.

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  • Pilot Study to Determine Radioiodide Accumulation and Dosimetry in Breast Cancers Using 124I PET/CT Not Recruiting

    This is a pilot imaging study for women whose tumors express NIS [Na+I- symporter, sodium iodide symporter]. Eligibility is limited to the presence of strong (3+) and/or plasma membrane staining in > 20% of cells as determined by immunohistochemical methods. A total of 10 patients will be imaged with 124I PET/CT (serial scans over 24 hour period) to determine radioiodide uptake and distribution in tumor tissue. Thyroid iodide uptake and retention will be blocked beginning one week prior to 124I PET/CT scan with thyroid hormone (T3) and methimazole (impedes organification). Tumor, organ and whole body dosimetry will be calculated in each patient.

    Stanford is currently not accepting patients for this trial. For more information, please contact Marilyn Florero, (650) 724 - 1953.

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  • Radioactive Iodide (131I) Treatment of 124I PET/CT Detected Breast Cancers Not Recruiting

    This is a treatment protocol designed to accompany the ongoing institutional 124I PET/CT pilot imaging study for patients with invasive breast cancer. Women whose tumors express NIS [Na+I- symporter, sodium iodide symporter] and demonstrate radioiodide uptake on 124I PET/CT scans will be eligible for 131I treatment if, (1) tumor dosimetry calculations yield a cumulative radiation dose of at least 30Gy in target tumor, (2) estimated cumulative thyroid irradiation is less than 500 cGy and, (3) the therapeutic dose of 131I is in the range of 25 to 100 mCi.

    Stanford is currently not accepting patients for this trial. For more information, please contact Marilyn Florero, (650) 724 - 1953.

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  • Study for Women With Platinum Resistant Ovarian Cancer Evaluating EC145 in Combination With Doxil® (PROCEED) Recruiting

    The purpose of this study is to compare progression-free survival (PFS) (based upon investigator assessment using RECIST v1.1) in participants with platinum-resistant ovarian cancer who receive combination therapy with EC145 and pegylated liposomal doxorubicin (EC145+PLD) with that in participants who receive PLD and placebo.

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Teaching

2013-14 Courses


Publications

Journal Articles


  • Safety of repeated yttrium-90 radioembolization. Cardiovascular and interventional radiology Lam, M. G., Louie, J. D., Iagaru, A. H., Goris, M. L., Sze, D. Y. 2013; 36 (5): 1320-1328

    Abstract

    PURPOSE: Repeated radioembolization (RE) treatments carry theoretically higher risk of radiation-induced hepatic injury because of the liver's cumulative memory of previous exposure. We performed a retrospective safety analysis on patients who underwent repeated RE. METHODS: From 2004 to 2011, a total of 247 patients were treated by RE. Eight patients (5 men, 3 women, age range 51-71 years) underwent repeated treatment of a targeted territory, all with resin microspheres (SIR-Spheres; Sirtex, Lane Cove, Australia). Adverse events were graded during a standardized follow-up. In addition, the correlation between the occurrence of RE-induced liver disease (REILD) and multiple variables was investigated in univariate and multivariate analyses in all 247 patients who received RE. RESULTS: Two patients died shortly after the second treatment (at 84 and 107 days) with signs and symptoms of REILD. Both patients underwent whole liver treatment twice (cumulative doses 3.08 and 2.66 GBq). The other 6 patients demonstrated only minor toxicities after receiving cumulative doses ranging from 2.41 to 3.88 GBq. All patients experienced objective tumor responses. In the whole population, multifactorial analysis identified three risk factors associated with REILD: repeated RE (p = 0.036), baseline serum total bilirubin (p = 0.048), and baseline serum aspartate aminotransferase (p = 0.043). Repeated RE proved to be the only independent risk factor for REILD in multivariate analysis (odds ratio 9.6; p = 0.002). Additionally, the administered activity per target volume (in GBq/L) was found to be an independent risk factor for REILD, but only in whole liver treatments (p = 0.033). CONCLUSION: The risk of REILD appears to be elevated for repeated RE. Objective tumor responses were observed, but establishment of safety limits will require improvement in dosimetric measurement and prediction.

    View details for DOI 10.1007/s00270-013-0547-9

    View details for PubMedID 23354961

  • Brain uptake of Tc99m-HMPAO correlates with clinical response to the novel redox modulating agent EPI-743 in patients with mitochondrial disease MOLECULAR GENETICS AND METABOLISM Blankenberg, F. G., Kinsman, S. L., Cohen, B. H., Goris, M. L., Spicer, K. M., Perlman, S. L., Krane, E. J., Kheifets, V., Thoolen, M., Miller, G., Enns, G. M. 2012; 107 (4): 690-699

    Abstract

    While decreased ATP production and redox imbalance are central to mitochondrial disease pathogenesis, efforts to develop effective treatments have been hampered by the lack of imaging markers of oxidative stress. In this study we wished to determine if Tc99m-HMPAO, a SPECT imaging marker of cerebral blood flow and glutathione/protein thiol content, could be used to monitor the effect(s) of EPI-743, an oral redox modulating, para-benzoquinone based therapeutic for mitochondrial disease. We hypothesized that treatment changes in HMPAO uptake would be inversely proportional to changes in oxidative stress within the brain and directly correlate to clinical response to EPI-743 therapy. Twenty-two patients with mitochondrial disease were treated with EPI-743. Each underwent baseline and 3-month Tc99m-HMPAO SPECT scanning along with clinical/neurologic evaluations. Diseases treated were: Leigh syndrome (n=7), polymerase ? deficiency (n=5), MELAS (n=5), Friedreich ataxia (n=2), Kearns-Sayre syndrome, Pearson syndrome, and mtDNA depletion syndrome. Neuro-anatomic uptake analyses of HMPAO were performed with NeuroGam™ (Segami Corp.) statistical software and clinical response was assessed by the Newcastle Paediatric Mitochondrial Disease Scale or Newcastle Mitochondrial Disease Adult Scale depending on patient age. For all 22 patients there was a significant linear correlation between the change in cerebellar uptake of HMPAO and the improvement in Newcastle score (r=0.623, **p=0.00161). The MELAS subgroup showed a significant relationship of whole brain uptake (n=5, r=0.917, *p=0.028) to improvement in Newcastle score. We conclude that Tc99m-HMPAO SPECT scanning has promise as a general marker of the oxidative state of the brain and its response to redox modulating therapies. Further studies will be needed to confirm these findings in a more homogenous study population.

    View details for DOI 10.1016/j.ymgme.2012.09.023

    View details for Web of Science ID 000311816200010

    View details for PubMedID 23084792

  • Positron Emission Tomography of Cu-64-DOTA-Rituximab in a Transgenic Mouse Model Expressing Human CD20 for Clinical Translation to Image NHL MOLECULAR IMAGING AND BIOLOGY Natarajan, A., Gowrishankar, G., Nielsen, C. H., Wang, S., Iagaru, A., Goris, M. L., Gambhir, S. S. 2012; 14 (5): 608-616

    Abstract

    This study aims to evaluate (64)Cu-DOTA-rituximab (PETRIT) in a preclinical transgenic mouse model expressing human CD20 for potential clinical translation.(64)Cu was chelated to DOTA-rituximab. Multiple radiolabeling, quality assurance, and imaging experiments were performed. The human CD20 antigen was expressed in B cells of transgenic mice (CD20TM). The mice groups studied were: (a) control (nude mice, n?=?3) that received 7.4 MBq/dose, (b) with pre-dose (CD20TM, n?=?6) received 2 mg/kg pre-dose of cold rituximab prior to PETRIT of 7.4 MBq/dose, and (c) without pre-dose (CD20TM, n?=?6) PETRIT alone received 7.4 MBq/dose. Small animal PET was used to image mice at various time points (0, 1, 2, 4, 24, 48, and 72 h). The OLINDA/EXM software was used to determine the human equivalent dose for individual organs.PETRIT was obtained with a specific activity of 545?±?38.91 MBq/nmole, radiochemical purity >95%, and immunoreactivity >75%. At 24 h, spleenic uptake of PETRIT%ID/g (mean?±?STD) with and without pre-dose was 1.76?±?0.43% and 16.5?±?0.45%, respectively (P value?=?0.01). Liver uptake with and without pre-dose was 0.41?±?0.51% and 0.52?±?0.17% (P value?=?0.86), respectively. The human equivalents of highest dose organs with and without pre-dose are osteogenic cells at 30.8?±?0.4 ?Sv/MBq and the spleen at 99?±?4 ?Sv/MBq, respectively.PET imaging with PETRIT in huCD20 transgenic mice provided human dosimetry data for eventual applications in non-Hodgkins lymphoma patients.

    View details for DOI 10.1007/s11307-011-0537-8

    View details for Web of Science ID 000308819300011

    View details for PubMedID 22231277

  • Targeted Systemic Radiotherapy with scVEGF/Lu-177 Leads to Sustained Disruption of the Tumor Vasculature and Intratumoral Apoptosis JOURNAL OF NUCLEAR MEDICINE Blankenberg, F. G., Levashova, Z., Goris, M. G., Hamby, C. V., Backer, M. V., Backer, J. M. 2011; 52 (10): 1630-1637

    Abstract

    Tumor vessels abundantly express receptors for vascular endothelial growth factor (VEGF), despite treatment with conventional or antiangiogenic drugs. We wished to determine whether the high levels of VEGF receptor (VEGFR) within the tumor vasculature could be leveraged for intracellular delivery of therapeutically significant doses of scVEGF/(177)Lu, a novel radiopharmaceutical based on a recombinant single-chain (sc) derivative of VEGF, in orthotopic breast cancer models.scVEGF-PEG (polyethylene gycol)-DOTA conjugates containing 2.0-, 3.4-, or 5.0-kDa PEG linkers site-specifically conjugated to a cysteine-containing tag (Cys-tag) in scVEGF were radiolabeled with (177)Lu (scVEGF/(177)Lu) for in vivo studies. Human MDA231luc and mouse 4T1luc cell lines were injected orthotopically to establish breast carcinoma tumors in immunodeficient and immunocompetent hosts, respectively. The effects of scVEGF/(177)Lu were defined by analysis of changes in tumor growth and immunohistochemical staining for the endothelial markers CD31 and VEGFR-2 and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining for intratumoral apoptosis.Biodistribution assays and dosimetric calculations established that scVEGF/(177)Lu with a 3.4-kDa PEG linker delivered the highest dose of radiation to tumors (69.9 cGy/MBq/g of tissue) and the lowest dose to the kidneys (33.3 cGy/MBq/organ). Total doses below 40 MBq/mouse of scVEGF/(177)Lu did not affect renal function, and 3 divided doses of 6.3 MBq/mouse or a bolus dose of 18.9 MBq/mouse induced only transient lymphopenia and weight loss (<10% baseline weight). In mice with orthotopic mammary breast carcinoma, intravenous injections of well-tolerated bolus and fractionated doses of scVEGF/(177)Lu in the range from 6.3 to 18.9 MBq/mouse (25-76 MBq/m(2)) resulted in dose-dependent tumor growth inhibition. Immunohistochemical analysis of tumors at 4-5 wk after single injections of scVEGF/(177)Lu indicated dose-dependent regression of tumor vasculature and widespread intratumoral apoptosis. A single dose of 7.4 MBq/mouse of scVEGF/(177)Lu given before a course of bevacizumab or sunitinib treatment enhanced the antiangiogenic effects of both drugs.Selective targeting of VEGFR in tumor vasculature with well-tolerated doses of scVEGF/(177)Lu is effective in orthotopic breast cancer models. As high levels of VEGFR expression in the tumor vasculature are a common feature in a variety of cancers, targeting tumor angiogenesis with scVEGF/(177)Lu warrants further exploration.

    View details for DOI 10.2967/jnumed.111.091629

    View details for Web of Science ID 000295537800023

    View details for PubMedID 21890879

  • Pilot Pharmacokinetic and Dosimetric Studies of F-18-FPPRGD2: A PET Radiopharmaceutical Agent for Imaging alpha(v)beta(3) Integrin Levels RADIOLOGY Mittra, E. S., Goris, M. L., Iagaru, A. H., Kardan, A., Burton, L., Berganos, R., Chang, E., Liu, S., Shen, B., Chin, F. T., Chen, X., Gambhir, S. S. 2011; 260 (1): 182-191

    Abstract

    To assess the safety, biodistribution, and dosimetric properties of the positron emission tomography (PET) radiopharmaceutical agent fluorine 18 ((18)F) FPPRGD2 (2-fluoropropionyl labeled PEGylated dimeric RGD peptide [PEG3-E{c(RGDyk)}2]), which is based on the dimeric arginine-glycine-aspartic acid (RGD) peptide sequence and targets ?(v)?(3) integrin, in the first volunteers imaged with this tracer.The protocol was approved by the institutional review board, and written informed consent was obtained from all participants. Five healthy volunteers underwent whole-body combined PET-computed tomography 0.5, 1.0, 2.0, and 3.0 hours after tracer injection (mean dose, 9.5 mCi ± 3.4 [standard deviation] [351.5 MBq ± 125.8]; mean specific radioactivity, 1200 mCi/mmol ± 714 [44.4 GBq/mmol ± 26.4]). During this time, standard vital signs, electrocardiographic (ECG) readings, and blood sample values (for chemistry, hematologic, and liver function tests) were checked at regular intervals and 1 and 7 days after the injection. These data were used to evaluate tracer biodistribution and dosimetric properties, time-activity curves, and the stability of laboratory values. Significant changes in vital signs and laboratory values were evaluated by using a combination of population-averaged generalized estimating equation regression and exact paired Wilcoxon tests.The administration of (18)F-FPPRGD2 was well tolerated, with no marked effects on vital signs, ECG readings, or laboratory values. The tracer showed the same pattern of biodistribution in all volunteers: primary clearance through the kidneys (0.360 rem/mCi ± 0.185 [0.098 mSv/MBq ± 0.050]) and bladder (0.862 rem/mCi ± 0.436 [0.233 mSv/MBq ± 0.118], voiding model) and uptake in the spleen (0.250 rem/mCi ± 0.168 [0.068 mSv/MBq ± 0.046]) and large intestine (0.529 rem/mCi ± 0.236 [0.143 mSv/MBq ± 0.064]). The mean effective dose of (18)F-FPPRGD2 was 0.1462 rem/mCi ± 0.0669 (0.0396 mSv/MBq ± 0.0181). With an injected dose of 10 mCi (370 MBq) and a 1-hour voiding interval, a patient would be exposed to an effective radiation dose of 1.5 rem (15 mSv). Above the diaphragm, there was minimal uptake in the brain ventricles, salivary glands, and thyroid gland. Time-activity curves showed rapid clearance from the vasculature, with a mean 26% ± 17 of the tracer remaining in the circulation at 30 minutes and most of the activity occurring in the plasma relative to cells (mean whole blood-plasma ratio, 0.799 ± 0.096).(18)F-FPPRGD2 has desirable pharmacokinetic and biodistribution properties. The primary application is likely to be PET evaluation of oncologic patients-especially those with brain, breast, or lung cancer. Specific indications may include tumor staging, identifying patients who would benefit from antiangiogenesis therapy, and separating treatment responders from nonresponders early.

    View details for DOI 10.1148/radiol.11101139

    View details for Web of Science ID 000291932300021

    View details for PubMedID 21502381

  • I-131-Tositumomab (BexxarA (R)) vs. Y-90-Ibritumomab (ZevalinA (R)) Therapy of Low-Grade Refractory/Relapsed Non-Hodgkin Lymphoma MOLECULAR IMAGING AND BIOLOGY Iagaru, A., Mittra, E. S., Ganjoo, K., Knox, S. J., Goris, M. L. 2010; 12 (2): 198-203

    Abstract

    The American Cancer Society estimated 66,120 new cases of non-Hodgkin lymphoma (NHL) in the USA in 2008. Radioimmunotherapy has been shown in clinical trials to be an effective treatment for refractory/relapsed NHL. The available agents are Bexxar, a (131)I radiolabeled murine monoclonal antibody, and Zevalin, a (90)Y radiolabeled murine antibody. Both target CD20 receptors present on the surface of lymphocytes. We present our clinical experience with Bexxar and Zevalin in the management of low-grade refractory or relapsed NHL.This is a retrospective study (Jan 2000-Jul 2006) of 67 patients with NHL, who were treated with Bexxar (31 patients, group A) or Zevalin (36 patients, group B) for refractory/relapsed disease. Group A included 16 men and 15 women, 35-81 years old (average, 59.3 +/- 13.4). Group B included 27 men and nine women, 36-85 years old (average, 55.4 +/- 13.8). Therapeutic doses ranged 40-138 mCi (average, 78.1 +/- 28.2) for Bexxar and 17-34 mCi (average, 28.8 +/- 4.37) for Zevalin.Objective responses were induced in 22 of the 31 patients (70.9%) in group A and 28 of the 36 patients (77.8%) in group B. Complete response was noted in 11 patients (35.5%), partial response in seven patients (22.6%), and mixed response in four patients (12.9%) in group A. There were five patients (16.1%) with stable disease and four patients (12.9%) with disease progression in the same group. Complete response was noted in 15 patients (41.7%), partial response in nine patients (25%), and mixed response in four patients (11.1%) in group B. There were four patients (11.1%) with stable disease and another four patients (11.1%) with disease progression in the same group. The average decreases at posttherapy nadir were 36.9% +/- 0.33 (group A) and 52.6% +/- 0.32 (group B) for platelets, 27.8% +/- 0.27 (group A) and 34.2% +/- 0.38 (group B) for leukocytes, and 4.9% +/- 0.15 (group A) and 7.6% +/- 0.11 (group B) for hemoglobin. Grades 3 and 4 hematological toxicity occurred in 14 patients (45.2%) treated with Bexxar and 22 patients (61.1%) treated with Zevalin, but was reversible.Our study suggests that clinical practice of Bexxar and Zevalin radioimmunotherapy is an effective and safe adjunctive treatment for patients with NHL refractory/relapsed to conventional treatment. However, due to the small number of subjects, it was not possible to determine whether differences in the outcomes or toxicities from the two agents were statistically significant.

    View details for DOI 10.1007/s11307-009-0245-9

    View details for Web of Science ID 000275974900010

    View details for PubMedID 19543946

  • Incorporating Cone-beam CT into the Treatment Planning for Yttrium-90 Radioembolization JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY Louie, J. D., Kothary, N., Kuo, W. T., Hwang, G. L., Hofmann, L. V., Goris, M. L., Iagaru, A. H., Sze, D. Y. 2009; 20 (5): 606-613

    Abstract

    To prepare for yttrium-90 ((90)Y) microsphere radioembolization therapy, digital subtraction angiography (DSA) and technetium- 99m-labeled macroaggregated albumin ((99m)Tc MAA) scintigraphy are used for treatment planning and detection of potential nontarget embolization. The present study was performed to determine if cone-beam computed tomography (CBCT) affects treatment planning as an adjunct to these conventional imaging modalities.From March 2007 to August 2008, 42 consecutive patients (21 men, 21 women; mean age, 59 years; range, 21-75 y) who underwent radioembolization were evaluated by CBCT in addition to DSA and (99m)Tc MAA scintigraphy during treatment planning, and their records were retrospectively reviewed. The contrast-enhanced territories shown by CBCT with selective intraarterial contrast agent administration were used to predict intrahepatic and possible extrahepatic distribution of microspheres.In 22 of 42 cases (52%), extrahepatic enhancement or incomplete tumor perfusion seen on CBCT affected the treatment plan. In 14 patients (33%), the findings were evident exclusively on CBCT and not detected by DSA. When comparing CBCT versus (99m)Tc MAA scintigraphy, CBCT showed eight cases of extrahepatic enhancement (19%) that were not evident on (99m)Tc MAA imaging. CBCT findings directed the additional embolization of vessels or repositioning of the catheter for better contrast agent and microsphere distribution. One case of gastric ulcer from nontarget embolization caused by reader error was observed.CBCT can provide additional information about tumor and tissue perfusion not currently detectable by DSA or (99m)Tc MAA imaging, which should optimize (90)Y microsphere delivery and reduce nontarget embolization.

    View details for DOI 10.1016/j.jvir.2009.01.021

    View details for Web of Science ID 000265700900007

    View details for PubMedID 19345589

  • Novel Strategy for a Cocktail F-18-Fluoride and F-18-FDG PET/CT Scan for Evaluation of Malignancy: Results of the Pilot-Phase Study JOURNAL OF NUCLEAR MEDICINE Iagaru, A., Mittra, E., Yaghoubi, S. S., Dick, D. W., Quon, A., Goris, M. L., Gambhir, S. S. 2009; 50 (4): 501-505

    Abstract

    (18)F-FDG PET/CT is used for detecting cancer and monitoring cancer response to therapy. However, because of the variable rates of glucose metabolism, not all cancers are identified reliably. Sodium (18)F was previously used for bone imaging and can be used as a PET/CT skeletal tracer. The combined administration of (18)F and (18)F-FDG in a single PET/CT study for cancer detection has not been reported to date.This is a prospective pilot study (November 2007-November 2008) of 14 patients with proven malignancy (6 sarcoma, 3 prostate cancer, 2 breast cancer, 1 colon cancer, 1 lung cancer, and 1 malignant paraganglioma) who underwent separate (18)F PET/CT and (18)F-FDG PET/CT and combined (18)F/(18)F-FDG PET/CT scans for the evaluation of malignancy (a total of 3 scans each). There were 11 men and 3 women (age range, 19-75 y; average, 50.4 y).Interpretation of the combined (18)F/(18)F-FDG PET/CT scans compared favorably with that of the (18)F-FDG PET/CT (no lesions missed) and the (18)F PET/CT scans (only 1 skull lesion seen on an (18)F PET/CT scan was missed on the corresponding combined scan). Through image processing, the combined (18)F/(18)F-FDG scan yielded results for bone radiotracer uptake comparable to those of the (18)F PET/CT scan performed separately.Our pilot-phase prospective trial demonstrates that the combined (18)F/(18)F-FDG administration followed by a single PET/CT scan is feasible for cancer detection. This combined method opens the possibility for improved patient care and reduction in health care costs.

    View details for DOI 10.2967/jnumed.108.058339

    View details for Web of Science ID 000272487200003

    View details for PubMedID 19289439

  • Endogenous NIS Expression in Triple-Negative Breast Cancers ANNALS OF SURGICAL ONCOLOGY Renier, C., Yao, C., Goris, M., Ghosh, M., Katznelson, L., Nowles, K., Gambhir, S. S., Wapnir, I. 2009; 16 (4): 962-968

    Abstract

    The sodium iodide symporter (NIS) mediates iodide transport into cells and has been identified in approximately 70% of breast cancers. Functional NIS expression raises the possibility of using (131)I for therapeutic targeting of tumor cells. Treatment of triple-negative breast cancers [estrogen/progesterone receptor-negative and HER2-negative (ER-/PR-/HER2-)] is primarily limited to chemotherapy. Our aim was to characterize NIS expression in this subset of tumors.Archival tissue sections from 23 women with triple-negative breast cancer were analyzed for NIS expression using immunohistochemical methods and an anti-human NIS antibody. Tumors were evaluated for the presence of plasma membrane immunoreactivity. One patient with a NIS-expressing positive tumor underwent (123)I scintigraphic imaging with dosimetric analysis.Fifteen cases (65.2%) demonstrated NIS-positivity with 11 tumors (47.8%) exhibiting strong expression. Plasma membrane immunoreactivity was observed in four breast cancers and was equivocal in another four tumors. Tumor-specific radioiodide uptake was demonstrated by (123)I scintigraphy in a patient with a large primary breast cancer unresponsive to neoadjuvant therapy. The tumor concentrated 2.05, 1.53, and 1.96 times more isotope than normal breast tissue at 1, 5, and 21 h. The relative increased uptake is consistent with positive NIS expression in the tumor on definitive surgery; however, the cumulative concentration in the tumor was not sufficient to achieve a therapeutic effect, had the isotope been (131)I.NIS is strongly expressed in a significant proportion of triple-negative breast cancer cells, suggesting a potential role for NIS-directed (131)I-radioablative strategies in this patient population.

    View details for DOI 10.1245/s10434-008-0280-9

    View details for Web of Science ID 000263976000026

    View details for PubMedID 19184238

  • Quantitative Analysis of Longitudinal Response to Aerosolized Granulocyte-Macrophage Colony-Stimulating Factor in Two Adolescents With Autoimmune Pulmonary Alveolar Proteinosis CHEST Robinson, T. E., Trapnell, B. C., Goris, M. L., Quittell, L. M., Cornfield, D. N. 2009; 135 (3): 842-848

    Abstract

    Autoimmune pulmonary alveolar proteinosis (APAP) is characterized by autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) in blood and tissues, resulting in alveolar surfactant protein accumulation. Patients with APAP present with ground-glass opacities (GGOs) and interlobular septal thickening on thin-slice chest CT scans. Aerosolized GM-CSF therapy (aeroGM-SCF) has qualitatively improved the clinical condition of patients with APAP. This report details quantitative chest CT responses to aeroGM-CSF.Two adolescent patients (aged 16 and 19 years) with APAP were treated with aeroGM-CSF. Clinical parameters, including pulmonary function tests and chest CT scans, were obtained before and after aeroGM-CSF therapy. To evaluate the effect of the therapy, serial chest CT scans were analyzed using a novel approach permitting quantitative assessment of improvement in GGOs, lung weight, and gas volume.In association with GM-CSF treatment, nutritional status and pulmonary function improved. Quantitative analysis of the CT scans demonstrated reduction in GGOs and lung weight, concomitant with an increase in airspace volume and lung inflation. The findings were consistent with a qualitative reduction in GGOs on chest CT imaging.Quantitative analysis of CT holds promise as a sensitive diagnostic tool permitting longitudinal and objective analysis of the therapeutic response to aeroGM-CSF in patients with APAP.

    View details for DOI 10.1378/chest.08-1317

    View details for Web of Science ID 000264310500034

    View details for PubMedID 19265094

  • Sampling density for the quantitative evaluation of air trapping PEDIATRIC RADIOLOGY Goris, M. L., Robinson, T. E. 2009; 39 (3): 221-225

    Abstract

    Concerns have been expressed recently about the radiation burden on patient populations, especially children, undergoing serial radiological testing. To reduce the dose one can change the CT acquisition settings or decrease the sampling density.In this study we determined the minimum desirable sampling density to ascertain the degree of air trapping in children with cystic fibrosis.Ten children with cystic fibrosis in stable condition underwent a volumetric spiral CT scan. The degree of air trapping was determined by an automated algorithm for all slices in the volume, and then for 1/2, 1/4, to 1/128 of all slices, or a sampling density ranging from 100% to 1% of the total volume. The variation around the true value derived from 100% sampling was determined for all other sampling densities.The precision of the measurement remained stable down to a 10% sampling density, but decreased markedly below 3.4%.For a disease marker with the regional variability of air trapping in cystic fibrosis, regardless of observer variability, a sampling density below 10% and even more so, below 3.4%, apparently decreases the precision of the evaluation.

    View details for DOI 10.1007/s00247-008-1076-6

    View details for Web of Science ID 000263097600005

    View details for PubMedID 19096836

  • Y-90-Ibritumomab Therapy in Refractory Non-Hodgkin's Lymphoma: Observations from In-111-Ibritumomab Pretreatment Imaging JOURNAL OF NUCLEAR MEDICINE Iagaru, A., Gambhir, S. S., Goris, M. L. 2008; 49 (11): 1809-1812

    Abstract

    Radioimmunotherapy is an effective treatment for non-Hodgkin's lymphoma (NHL). 90Y-ibritumomab is an antibody targeting CD20 receptors on the surface of lymphocytes. We present observations from our clinical experience with 90Y-ibritumomab in the management of NHL.This was a retrospective study of 28 NHL patients treated with 90Y-ibritumomab. There were 21 men and 7 women, 36-85 y old. A diagnostic dose of 111In-ibritumomab was administered on day 0, and imaging followed immediately and at 24, 48, and 72 h. The doses of 90Y-ibritumomab ranged from 629 to 1,258 MBq (17-34 mCi). Outcomes were compared with the findings of the 111In-ibritumomab scans.90Y-ibritumomab induced objective responses in 22 of 28 patients. A complete response was noted in 9 patients, a partial response in 9 patients, and a mixed response in 4 patients. Three patients had stable disease, and 3 patients had disease progression. 111In-ibritumomab findings were positive in 19 patients and negative in 9 patients. A complete response was noted in 2 of 19 patients with positive findings and 7 of 9 with negative findings. A partial response was seen in 7 of 19 patients with positive findings and 1 of 9 with negative findings. Disease progression was observed in 3 of 19 patients with positive findings and 0 of 9 with negative findings. The remaining patients had a mixed response or no changes.A higher rate of complete response after 90Y-ibritumomab treatment was seen in patients with negative 111In-ibritumomab findings, whereas a higher rate of disease progression despite therapy was noted in patients with positive 111In-ibritumomab findings. This observation suggests that patients with bulky disease may require more aggressive management.

    View details for DOI 10.2967/jnumed.108.052928

    View details for Web of Science ID 000260846600019

    View details for PubMedID 18927323

  • F-18-FDG-PET/CT evaluation of response to treatment in lymphoma: when is the optimal time for the first re-evaluation scan? HELLENIC JOURNAL OF NUCLEAR MEDICINE Iagaru, A., Wang, Y., Mari, C., Quon, A., Goris, M. L., Horning, S., Gambhir, S. S. 2008; 11 (3): 153-156

    Abstract

    Assessing the response to treatment as soon after treatment initiation is one of the key reasons for imaging lymphoma patients. The optimal time after initiating treatment for assessing response to treatment has yet to be determined. Therefore, we were prompted to review our experience with serial (18)F-FDG PET/CT in patients undergoing treatment for Hodgkin's disease (HD) and non Hodgkin's lymphoma (NHL). This is a retrospective study (Feb 2003 - Oct 2004) of 20 patients, 11 men and 9 women, with age range of 7-75 years with diagnosis of HD (10) and NHL (10), who had PET/CT at our institution prior, during and at the completion of therapy. Restaging PET/CT was done after 2 cycles of chemotherapy in 10 patients (group A) and after 4 cycles of chemotherapy in 10 pts (group B). A total of 60 scans were reviewed. The DeltaSUV from baseline to first PET/CT was on average 67.6% in group A and 75.1% in group B. This had no statistical significance (P value: 0.31). The DeltaSUV from baseline to post-therapy PET/CT was on average 72.9% in group A and 79.8% in group B. This difference also had no statistical significance (P value: 0.24). The correlation coefficient was 0.98 in group A and 0.80 in group B. Results of PET/CT after 2 cycles of chemotherapy did not statistically differ from the results of PET/CT after 4 cycles of chemotherapy. These results need to be confirmed in larger, prospective, randomized trials.

    View details for Web of Science ID 000262093600003

    View details for PubMedID 19081857

  • Rhabdomyosarcoma diffusely metastatic to the bone marrow: suspicious findings on Tc-99m-MDP bone scintigraphy confirmed by F-18-18 FDG PET/CT and bone marrow biopsy EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Iagaru, A., Goris, M. L. 2008; 35 (9): 1746-1746

    View details for DOI 10.1007/s00259-008-0864-4

    View details for Web of Science ID 000258673800026

    View details for PubMedID 18648808

  • Perspectives of molecular imaging and radioimmunotherapy in lymphoma RADIOLOGIC CLINICS OF NORTH AMERICA Iagaru, A., Goris, M. L., Gambhir, S. S. 2008; 46 (2): 243-252

    Abstract

    Successful treatment of Hodgkin lymphomas and non-Hodgkin lymphomas depends on accurate staging and prognostic estimations, as well as evaluation of response to therapy as early after initiation as possible. We focus on several aspects of molecular imaging and therapy that affect the management of patients who have lymphoma. First, we review prior use of gallium-67 citrate for evaluation of lymphoma patients, mainly from a historical perspective, since it was the mainstream lymphoma functional imaging tracer for decades. Next, we review current clinical uses of 18F Fluoro-2-Deoxyglucose (18F FDG) PET and PET/CT for evaluation of lymphoma patients and use of radioimmunotherapy in lymphoma. Finally, we discuss advances in molecular imaging that may herald the next generation of PET radiotracers after 18F FDG.

    View details for DOI 10.1016/j.rcl.2008.03.007

    View details for Web of Science ID 000258543500006

    View details for PubMedID 18619379

  • Monitoring the protective effects of minocycline treatment with radiolabeled annexin v in an experimental model of focal cerebral ischemia JOURNAL OF NUCLEAR MEDICINE Tang, M. N., Wang, Q., Koikel, M. A., Cheng, D., Goris, M. L., Blankenberg, F. G., Yenari, M. A. 2007; 48 (11): 1822-1828

    Abstract

    Minocycline is an antibiotic now recognized to have antiapoptotic and antiinflammatory properties. Because of these properties, minocycline may be of benefit in reducing neuronal apoptosis from ischemia and subsequent postischemic inflammation if administered soon after a stroke. We now explore the feasibility of using (99m)Tc-annexin V, an in vivo marker of apoptosis, with SPECT to monitor the antiapoptotic effects of minocycline therapy.CB6/F1 adult male mice underwent unilateral distal middle cerebral artery occlusion (dMCA) occlusion and were imaged and sacrificed at 1, 3, 7, or 30 d after injury. Animals were given minocycline (or vehicle) 30 min and 12 h after dMCA occlusion and then given 22.5 mg/kg twice daily for up to 7 d. Before imaging, behavioral tests were performed to evaluate the neurologic function. After imaging, brains were collected for histology and assessed for the degree of apoptosis and microglial activation.(99m)Tc-Annexin V uptake in injured hemispheres was significantly decreased 2- to 3-fold by minocycline at all time points. Minocyline reduced infarct size as seen histologically and improved behavioral indices as late as 30 d. Infarct volume as seen histologically correlated with radiolabeled annexin V uptake seen by SPECT. In situ fluorescent microscopy demonstrated that annexin V bound primarily to neurons at 1 and 3 d, with a shift toward microglia by 7 and 30 d.We found that minocycline significantly reduces neuronal apoptosis and infarct size and improves neurologic outcome in mice after acute focal cortical ischemia.

    View details for DOI 10.2967/jnumed.107.041335

    View details for Web of Science ID 000252894900019

    View details for PubMedID 17942809

  • A critical discussion of computer analysis in medical imaging. Proceedings of the American Thoracic Society Goris, M. L., Zhu, H. J., Robinson, T. E. 2007; 4 (4): 347-349

    Abstract

    Medical imaging has increasingly provided surrogate endpoints in therapeutic trials. This use assumes that the interpretation of the images can be unbiased and reproducible and that the image attributes included in the interpretation are relevant to the mechanism of the trial. The principal motivation for computer analysis is to evaluate an attribute of the image as a metric in an algorithmic manner, independent of observer bias or variability. The metric is expected to reflect change in rough proportion with at least one aspect of the degree of disease or the effectiveness of the therapeutic intervention. If either condition is satisfied, the measure is quantitative. Visual interpretation explicitly or implicitly tends to be based on multiple image attributes. Explicit combination of multiple attributes yields composite scores. To evaluate the risk or probability of disease, they are useful. But the components of the scores can be combined only if they are mathematically isomorphic. For the evaluation of interventions, they are less useful because the effect on one component may be obscured by the lack of effect on other components. This article reviews quantification of air trapping in cystic fibrosis and quantification in general. Validation of any computer analysis can rely on agreement with visual interpreters (on average), they can be derived from first principles, or by agreement with an alternative method that measures the pathophysiological mechanism directly (xenon washout for air trapping). However, in the context of trials, the validation may come from a superior ability to detect objective change and to discriminate between affected and unaffected individuals.

    View details for PubMedID 17652499

  • Evaluation of herpes simplex virus 1 thymidine kinase-mediated trapping of I-131 FIAU and prodrug activation of ganciclovir as a synergistic cancer radio/chemotherapy MOLECULAR IMAGING AND BIOLOGY Schipper, M. L., Goris, M. L., Gambhir, S. S. 2007; 9 (3): 110-116

    Abstract

    Evaluation of selective killing of Herpes Simplex Virus 1 thymidine kinase (HSV1-tk) expressing tumors by radiolabeled (131)I-fialuridine (FIAU), and of synergy between (131)I-FIAU and Ganciclovir (GCV).HSV1-tk-expressing cell lines and parental cell lines were exposed to (131)I-FIAU alone, GCV alone, or combinations. Activity and concentration were varied widely, concurrent and sequential administrations tested, and dose rate effects were studied.HSV1-tk-expressing cells accumulated up to 15.7-fold more (131)I-FIAU, were growth inhibited by 2 muCi/ml, or 5 muCi/ml (131)I-FIAU, and were inhibited by two log orders lower concentrations of GCV than parental cells. However, no synergy or additive effect was observed. Dose rate variations, or sequential treatment, did not alter outcome.Radioisotope therapy of HSV1-tk-expressing tumor cells with (131)I-FIAU is reported for the first time. Lack of synergy between (131)I-FIAU and GCV does not warrant further investigation of combination treatment with the two agents.

    View details for DOI 10.1007/s11307-007-0078-3

    View details for Web of Science ID 000246175500003

    View details for PubMedID 17294333

  • Relative lung perfusion distribution in normal lung scans: observations and clinical implications. Congenital heart disease Cheng, C. P., Taur, A. S., Lee, G. S., Goris, M. L., Feinstein, J. A. 2006; 1 (5): 210-216

    Abstract

    While relative lung perfusion distributions are cited in clinical decision making for congenital and acquired pulmonary vascular diseases, normal values and ranges have not been published for a large population of normally perfused lungs. These values of normal relative perfusion will be useful for establishing what is abnormal and for clinical decisions related to various pulmonary vascular diseases.Relative perfusion distributions were quantified for the top, middle, and bottom thirds of the right and left lungs with a semiautomatic algorithm in 206 normal scintigraphy lung studies (45 +/- 18 years, 149 female, 57 male) acquired between January 1, 2000 and March 30, 2004 in the Nuclear Medicine Division at Stanford Hospital and Clinics.The perfusion data were found to be highly non-Gaussian in nature (necessitating the use of Wilcoxon statistical comparisons), and the right/left perfusion ratio was found to be 52.5/47.5 (+/-2.1%) rather than the often quoted 55/45 split. While this right/left split was consistent between the genders, males had proportionally less perfusion in the lower left lung as compared with females (P < .05).The long-standing 55/45 right/left perfusion ratio assumption was found to be more than 1 standard deviation greater than the mean, and the population variance is very small. Relative pulmonary perfusion distribution varies significantly with lung region, gender, and age, and should be considered when making clinical decisions based on pulmonary perfusion.

    View details for DOI 10.1111/j.1747-0803.2006.00037.x

    View details for PubMedID 18377528

  • Phase I study of I-131-chimeric(ch) TNT-1/B monoclonal antibody for the treatment of advanced colon cancer CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS Street, H. H., Goris, M. L., Fisher, G. A., Wessels, B. W., Cho, C., Hernandez, C., Zhu, H. J., Zhang, Y., Nangiana, J. S., Shan, J. S., Roberts, K., Knox, S. J. 2006; 21 (3): 243-256

    Abstract

    The primary aim of this study was to evaluate the biodistribution and toxicity of 131I-chimeric(ch) TNT-1/B monoclonal antibody (MAB), which binds to intracellular antigens of necrotic regions within tumors, in patients with advanced colon or colorectal cancer. The rationale for targeting areas of tumor necrosis is the observation that necrotic lesions are more abundant in cancer lesions than in surrounding tissues.Cohorts of patients with advanced colon or colorectal cancer were administered a one-time 30-60-minute intravenous (i.v.) infusion of 131I-chTNT-1/B at doses ranging from 12.95 to 66.23 MBq/kg (0.35-1.79 mCi/kg).The dose-limiting toxicity, experienced at 66.23 MBq/kg (1.79 mCi/kg) 131I-chTNT-1/B MAB, was myelosuppression. Two (2) patients at the 66.23-MBq/kg (1.79 mCi/kg) dose level had both grade 3 thrombocytopenia and grade 3 neutropenia that persisted for at least 2 weeks but were reversible. The maximum tolerated dose was 58.09 MBq/kg (1.57 mCi/kg) 131I-chTNT-1/B MAB. Of the 21 patients, one developed a moderate human antichimeric antibody (HACA) response and 6 developed low HACA responses.The infusion of 131I-chTNT-1/B MAB was well tolerated, without significant nonhematological toxicity. No patient obtained a complete or partial response, based on tumor cross-product response criteria. Tumor localization was seen in patients with dose levels at, and exceeding, 50.23 MBq/kg (1.36 mCi/kg) 131I-chTNT-1/B MAB.

    View details for Web of Science ID 000239162600010

    View details for PubMedID 16918301

  • Tc-99-HYNIC-annexin VSPECT imaging of acute stroke and its response to neuroprotective therapy with anti-Fas ligand antibody EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Blankenberg, F. G., Kalinyak, J., Liu, L. P., Koike, M., Cheng, D. Y., Goris, M. L., Green, A., Vanderheyden, J. L., Tong, D. C., Yenari, M. A. 2006; 33 (5): 566-574

    Abstract

    The first aim of the study was to determine whether (99m)Tc-HYNIC-annexin V, a marker of cellular stress and apoptosis, can detect ischemic injury in patients with acute stroke. Secondly, we wished to test radiolabeled annexin's ability to monitor therapy in a rodent model of focal ischemic injury.SPECT imaging of patients was performed between 1 and 2 h after intravenous injection of 30 mCi (1,110 MBq) of tracer. Eight MFL4 (anti-FasL) antibody-treated (400 microg i.p. days 0 and 3) and 21 control adult male Sprague-Dawley rats underwent small animal SPECT imaging with 5-10 mCi (185-370 MBq) of tracer, 1 and 6 days after a 2-h intraluminal thread occlusion of the left middle cerebral artery.Two patients with acute stroke had regions of multifocal annexin uptake that correlated with sites of restricted diffusion on MRI. Anti-FasL antibody treatment significantly reduced annexin uptake by 92% with a 60% decrease in the number of caspase-8 staining (apoptotic) neurons on day 1. On day 6, treated animals had an 80% reduction in tracer uptake with a 75% decrease in infarct size as compared with controls. Annexin uptake in controls and treated animals (day 6) linearly correlated with infarct size (r (2)=0.603, p=0.0036) and the number of TUNEL-positive (apoptotic) nuclei (r (2)=0.728, p=0.00084).Annexin imaging shows foci of increased uptake at sites of ischemic injury in patients with acute stroke. Annexin imaging can assess the effects of therapy for ischemic cerebral injury in rats, suggesting its potential as a non-invasive indicator of drug efficacy in future clinical trials.

    View details for DOI 10.1007/s00259-005-0046-6

    View details for Web of Science ID 000237324100009

    View details for PubMedID 16477433

  • Bioluminescent-inescent monitoring of NIS-mediated I-131 ablative effects in MCF-7 Xenografts MOLECULAR IMAGING Ghosh, M., Gambhir, S. S., De, A., Nowels, K., Goris, M., Wapnir, I. 2006; 5 (2): 76-84

    Abstract

    Optical imaging has made it possible to monitor response to anticancer therapies in tumor xenografts. The concept of treating breast cancers with (131)I is predicated on the expression of the Na(+)/I- symporter (NIS) in many tumors and uptake of I- in some. The pattern of (131)I radioablative effects were investigated in an MCF-7 xenograft model dually transfected with firefly luciferase and NIS genes. On Day 16 after tumor cell implantation, 3 mCi of (131)I was injected. Bioluminescent imaging using d-luciferin and a cooled charge-coupled device camera was carried out on Days 1, 2, 3, 7, 10, 16, 22, 29, and 35. Tumor bioluminescence decreased in (131)I-treated tumors after Day 3 and reached a nadir on Day 22. Conversely, bioluminescence steadily increased in controls and was 3.85-fold higher than in treated tumors on Day 22. Bioluminescence in (131)I-treated tumors increased after Day 22, corresponding to tumor regrowth. By Day 35, treated tumors were smaller and accumulated 33% less (99m)TcO(4)(-) than untreated tumors. NIS immunoreactivity was present in <50% of (131)I-treated cells compared to 85-90% of controls. In summary, a pattern of tumor regression occurring over the first three weeks after (131)I administration was observed in NIS-expressing breast cancer xenografts.

    View details for DOI 10.2310/7290.2006.00008

    View details for Web of Science ID 000239285900004

    View details for PubMedID 16954021

  • Dornase alfa reduces air trapping in children with mild cystic fibrosis lung disease - A quantitative analysis CHEST Robinson, T. E., Goris, M. L., Zhu, H. J., Chen, X. R., Bhise, F., Sheikh, F., Moss, R. B. 2005; 128 (4): 2327-2335

    Abstract

    To evaluate quantitative air trapping measurements in children with mild cystic fibrosis (CF) lung disease during a 1-year, double-blind, placebo-controlled, recombinant human deoxyribonuclease (rhDNase) [dornase alfa] intervention trial and compare results from quantitative air trapping with those from spirometry or visually scored high-resolution CT (HRCT) scans of the chest.Twenty-five children with CF randomized to either daily rhDNase or placebo aerosol were evaluated at baseline, and at 3 months and 12 months by spirometer-triggered HRCT and spirometry. Outcome variables were percentage of predicted FVC, FEV1, and forced expiratory flow, midexpiratory phase (FEF(25-75%)); total and subcomponent visual HRCT scores; and quantitative air trapping measurements derived from chest HRCT images.At baseline, there were no statistical differences between groups in any of the variables used as an outcome. After 3 months of treatment, both groups had improvements in percentage of predicted FEV1 and FEF(25-75%), and total HRCT visual scores. In contrast, the rhDNase group had a 13% decrease in quantitative air trapping from baseline (severe air trapping [A3]), compared to an increase of 48% in the placebo group (p = 0.023). After 12 months, both groups had declines in percentage of predicted FVC and FEV1, but the rhDNase group retained improvements in percentage of predicted FEF(25-75%) and quantitative air trapping. The mucus plugging and total HRCT visual scores were also improved in the rhDNase group after 12 months of treatment, with and without significant differences between groups (p = 0.026 and p = 0.676). Quantitative air trapping (A3) remained improved in the rhDNase group (- 15.4%) and worsened in the placebo group (+61.3%) with nearly significant differences noted between groups (p = 0.053) after 12 months of treatment.Quantitative air trapping is a more consistent sensitive outcome measure than either spirometry or total HRCT scores, and can discriminate differences in treatment effects in children with minimal CF lung disease.

    View details for Web of Science ID 000232679400063

    View details for PubMedID 16236891

  • Efficacy and safety of tositumomab and iodine-131 tositumomab (Bexxar) in B-Cell lymphoma, progressive after rituximab JOURNAL OF CLINICAL ONCOLOGY Horning, S. J., Younes, A., Jain, V., KROLL, S., Lucas, J., Podoloff, D., Goris, M. 2005; 23 (4): 712-719

    Abstract

    To determine overall response (OR) and complete response (CR) rates, response duration, progression-free (PFS) and overall survival and safety with the tositumomab and iodine-131 tositumomab ((131)I tositumomab) therapeutic regimen in patients with indolent, follicular large-cell, or transformed B-cell lymphoma, progressive after rituximab.From July 1998 to November 1999, 40 patients (24 rituximab nonresponders: 11 with response < 6 months, and five with response > or = 6 months) received a therapeutic dose (0.65 to 0.75 Gy per platelet count) of (131)I tositumomab based on total-body dosimetry in this prospective phase II study. The median number of prior treatments was four; 59% of patients were chemotherapy-resistant.Confirmed OR (65%) and CR (38%) rates were not significantly associated with prior rituximab response. With a median follow-up of 3.3 years, the median PFS was 10.4 months, 24.5 months for responders, and not reached for CR patients. Among follicular grade 1 or 2 patients with tumors < or = 7 cm (n = 21), the OR and CR rates were 86% and 57%. Estimated 3-year PFS in this subgroup was 48%, compared with 11% for all others (P = .002). Transient grade 3 to 4 marrow toxicity was seen in 50% of patients. Two patients, one of whom received two subsequent chemotherapy regimens, developed secondary myelodysplasia.(131)I tositumomab is effective in CD20-positive lymphoma progressive after rituximab, with a 65% OR rate and median PFS of 24.5 months for responders. Patients with follicular grade 1 or 2 histology and tumors < or = 7 cm achieved very high OR and CR rates, with 48% PFS at 3 years.

    View details for DOI 10.1200/JCO.2005.07.040

    View details for Web of Science ID 000226738900010

    View details for PubMedID 15613695

  • The radioisotope contributes significantly to the activity of radioimmunotherapy CLINICAL CANCER RESEARCH Davis, T. A., Kaminski, M. S., Leonard, J. P., Hsu, F. J., Wilkinson, M., Zelenetz, A., Wahl, R. L., KROLL, S., Coleman, M., Goris, M., Levy, R., Knox, S. J. 2004; 10 (23): 7792-7798

    Abstract

    A multicenter, randomized study was undertaken to estimate the single agent activity of Tositumomab and to determine the contribution of radioisotope-labeling with (131)I to activity and toxicity by comparing treatment outcomes for Tositumomab and Iodine I 131 Tositumomab (BEXXAR) to an equivalent total dose of unlabeled Tositumomab.Seventy-eight patients with refractory/relapsed non-Hodgkin's lymphoma were randomized to either unlabeled Tositumomab or Iodine I 131 Tositumomab. Patients progressing after unlabeled Tositumomab could cross over to receive Iodine I 131 Tositumomab. The median follow-up at analysis was 42.6 months (range 1.9 to 71.5 months).Responses in the Iodine I 131 Tositumomab versus unlabeled Tositumomab groups: overall response 55% versus 19% (P = 0.002); complete response 33% versus 8% (P = 0.012); median duration of overall response not reached versus 28.1 months (95% confidence interval: 7.6, not reached); median duration of complete response not reached in either arm; and median TTP 6.3 versus 5.5 months (P = 0.031), respectively. Of the patients who had a complete response after initial Iodine I 131 Tositumomab therapy, 71% (10 of 14) continued in complete response at 29.8 to 71.1 months. Two patients who achieved a complete response after unlabeled Tositumomab had ongoing responses at 48.1 to 56.9 months. Nineteen patients received Iodine I 131 Tositumomab crossover therapy. Responses after crossover versus prior response to unlabeled Tositumomab were as follows: complete response rates of 42% versus 0% (P = 0.008); overall response 68% versus 16% (P = 0.002); median durations of overall response 12.6 versus 7.6 months (P = 0.001); and median TTP 12.4 versus 5.5 months (P = 0.01), respectively. Hematologic toxicity was more severe and nonhematologic adverse events were more frequent after Iodine I 131 Tositumomab than after Tositumomab alone. Elevated thyrotropin occurred in 5% of patients. Seroconversion to human antimurine antibody after Iodine I 131 Tositumomab, unlabeled Tositumomab, and Iodine I 131 Tositumomab-crossover was 27%, 19%, and 0%, respectively.Unlabeled Tositumomab showed single agent activity, but in this direct comparison, all of the therapeutic outcome measures were significantly enhanced by the conjugation of (131)I to Tositumomab.

    View details for Web of Science ID 000225673200002

    View details for PubMedID 15585610

  • Pericardial lymph node involvement in lymphoma as identified on PET CLINICAL NUCLEAR MEDICINE Franc, B., Yoshida, E., Herfkens, R., Goris, M. 2004; 29 (11): 741-742

    View details for Web of Science ID 000224716000021

    View details for PubMedID 15483497

  • The Na+/I- symporter mediates iodide uptake in breast cancer metastases and can be selectively down-regulated in the thyroid CLINICAL CANCER RESEARCH Wapnir, I. L., Goris, M., Yudd, A., Dohan, O., Adelman, D., Nowels, K., Carrasco, N. 2004; 10 (13): 4294-4302

    Abstract

    The Na(+)/I(-) symporter (NIS) is a key plasma membrane protein that mediates active iodide (I(-)) transport in the thyroid, lactating breast, and other tissues. Functional NIS expression in thyroid cancer accounts for the longstanding success of radioactive iodide ((131)I) ablation of metastases after thyroidectomy. Breast cancer is the only other cancer demonstrating endogenous functional NIS expression. Until now, NIS activity in breast cancer metastases (BCM) was unproven.Twenty-seven women were scanned with (99m)TcO(4)(-) or (123)I(-) to assess NIS activity in their metastases. An (131)I dosimetry study was offered to patients with I(-)-accumulating tumors. Selective down-regulation of thyroid NIS was tested in 13 patients with T(3) and in one case with T(3) + methimazole (MMI; blocks I(-) organification). NIS expression was evaluated in index and/or metastatic tumor samples by immunohistochemistry.I(-) uptake was noted in 25% of NIS-expressing tumors (two of eight). The remaining cases did not show NIS expression or activity. Thyroid I(-) uptakes were decreased to

    View details for Web of Science ID 000222457300002

    View details for PubMedID 15240514

  • Detection of focal hypoxic-ischemic injury and neuronal stress in a rodent model of unilateral MCA occlusion/reperfusion using radiolabeled annexin V EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Mari, C., Karabiyikoglu, M., Goris, M. L., Tait, J. F., Yenari, M. A., Blankenberg, F. G. 2004; 31 (5): 733-739

    Abstract

    In this study we wished to determine whether technetium-99m annexin V, an in vivo marker of cellular injury and death, could be used to noninvasively monitor neuronal injury following focal middle cerebral artery (MCA) occlusion/reperfusion injury. Sixteen adult male Sprague-Dawley rats (along with four controls) underwent left (unilateral) MCA intraluminal beaded thread occlusion for 2 h followed by reperfusion. One hour following tail vein injection of 5-10 mCi of (99m)Tc-annexin V, animals underwent either single-photon emission computerized tomography (SPECT) or autoradiography followed by immunohistochemical analyses. There was abnormal, bilateral, multifocal uptake of (99m)Tc-annexin V in each cerebral hemisphere as seen by both SPECT and autoradiography at 4 h and 1, 3, and 7 days after initiation of occlusion. The average maximal annexin V uptake at 4 h was 310%+/-85% and 365%+/-151% above control values (P<0.006) within the right and left hemispheres, respectively, peaking on day 3 with values of 925%+/-734% and 1,194%+/-643% (P<0.03) that decreased by day 7 to 489%+/-233% and 785%+/-225% (P<0.01). Total lesional volume of the left hemisphere was 226%, 261%, and 451% ( P<0.03) larger than the right at 4, 24, and 72 h after injury, respectively. Annexin V localized to the cytoplasm of injured neurons ipsilateral to the site of injury as well as to otherwise normal-appearing neurons of the contralateral hemisphere as confirmed by dual fluorescent microscopy. It is concluded that there is abnormal bilateral, multifocal annexin V uptake, greater on the left than on the right side, within 4 h of unilateral left MCA ischemic injury and that the uptake peaks at 3 days and decreases by 7 days after injury. This pattern suggests that neuronal stress may play a role in the response of the brain to focal injury and be responsible for annexin V uptake outside the region of ischemic insult.

    View details for DOI 10.1007/s00259-004-1473-5

    View details for Web of Science ID 000220880100017

    View details for PubMedID 14985868

  • An automated approach to quantitative air trapping measurements in mild cystic fibrosis CHEST Goris, M. L., Zhu, H. Y., Blankenberg, F., Chan, F., Robinson, T. E. 2003; 123 (5): 1655-1663

    Abstract

    To automatically derive the degree of air trapping in mild cystic fibrosis (CF) disease from high-resolution CT (HRCT) data, and to evaluate the discriminating power of the measurement.The data consist of six pairs of anatomically matched tomographic slices, obtained during breath-holding in triggered HRCT acquisitions. The pairs consist of an inspiratory slice, at > or = 95% of slow vital capacity, and an expiratory slice at near residual volume (nRV). The subjects are 25 patients with mild CF and 10 age-matched, normal control subjects.Lung segmentation is automatic. The limits defining air trapping in the expiratory slices are determined by the distribution of densities in the expanded lung. They are modulated by density changes between expiration and inspiration. Air trapping defects consist of contiguous low-density voxels. The difference between patients and control subjects was evaluated in comparison to pulmonary function test (PFT) results and lung density distribution descriptors (global density descriptors).In mild CF, air trapping does not correlate with global PFT results, except for the ratio of residual volume (RV) to total lung capacity (TLC); however, the size of air trapping defects was the best discriminator between patients and control subjects (p < 0.005). Of PFT results, only RV/TLC reached significance at p < 0.05. The global density descriptors reached near significance in the nRV images only.Air trapping defined as defect size and measured in an objective automated manner is a powerful discriminator for mild CF.

    View details for Web of Science ID 000182773000051

    View details for PubMedID 12740287

  • Positively labeled white blood cell scan with eosinophilia and absence of infection CLINICAL NUCLEAR MEDICINE Vasanawala, M. S., Goris, M. L. 2003; 28 (5): 389-391

    Abstract

    The authors describe the variability of Tc-99m exametazime-labeled leukocyte distribution as a function of the relative frequency of white cell types in the labeled blood.A 76-year-old man who was hospitalized with fever and possible postoperative osteomyelitis underwent scintigraphic imaging with Tc-99m exametazime-labeled leukocytes.The white cell scan excluded any discrete focus of infection and revealed diffuse involvement of the lymph nodes and skin. The pathologic diagnosis was angioimmunoblastic T-cell lymphoma. The atypical infiltrates seen on the white cell scan can be explained by the severe eosinophilic blood count on the day of leukocyte labeling (total leukocyte count: 8,100 cells/microl with 63% neutrophils, 8.9% lymphocytes, and 22.2% eosinophils).In the labeling of the leukocyte moiety, a higher presence of any leukocyte subpopulation will modify the biodistribution and thus the image interpretation.

    View details for Web of Science ID 000183386300005

    View details for PubMedID 12702935

  • Therapeutic lymphangiogenesis with human recombinant VEGF-C. FASEB journal Szuba, A., Skobe, M., Karkkainen, M. J., Shin, W. S., Beynet, D. P., Rockson, N. B., Dakhil, N., Spilman, S., Goris, M. L., Strauss, H. W., Quertermous, T., Alitalo, K., Rockson, S. G. 2002; 16 (14): 1985-1987

    Abstract

    Chronic regional impairments of the lymphatic circulation often lead to striking architectural abnormalities in the lymphedematous tissues. Lymphedema is a common, disabling disease that currently lacks a cure. Vascular endothelial growth factors C and D mediate lymphangiogenesis through the VEGFR-3 receptor on lymphatic endothelia. The purpose of this study was to investigate the therapeutic potential for lymphangiogenesis with VEGF-C. We developed a rabbit ear model to simulate human chronic postsurgical lymphatic insufficiency. Successful, sustained surgical ablation of the ear lymphatics was confirmed by water displacement volumetry. After complete healing, the experimental animals (n=8) received a single, s.c. 100 microg dose of VEGF-C in the operated ear; controls (n=8) received normal saline. Radionuclide lymphoscintigraphy was performed to quantitate lymphatic function. Immunohistochemistry (IHC) was performed 7-8 days following treatment. After VEGF-C, there was a quantifiable amelioration of lymphatic function. IHC confirmed a significant increase in lymphatic vascularity, along with reversal of the intense tissue hypercellularity of untreated lymphedema. This study confirms the capacity of a single dose of VEGF-C to induce therapeutic lymphangiogenesis in acquired lymphedema. In addition to improving lymphatic function and vascularity, VEGF-C can apparently reverse the abnormalities in tissue architecture that accompany chronic lymphatic insufficiency.

    View details for PubMedID 12397087

  • Low uptake of Tc-99m tetrofosmin in lung cancer - A case report CLINICAL NUCLEAR MEDICINE Franc, B., Goris, M. 2002; 27 (10): 698-700

    Abstract

    Technetium-99m tetrofosmin has been used as a tumor-imaging agent in cases of lung cancer. The authors present a case showing a lung tumor that concentrated Tl-201 distinctly more than Tc-99m tetrofosmin during a dual-isotope cardiac examination. A brief review of the literature is provided and possible explanations for this difference in tracer uptake are discussed.

    View details for DOI 10.1097/01.RLU.0000027801.86894.5D

    View details for Web of Science ID 000178268400002

    View details for PubMedID 12352109

  • Therapeutic lymphangiogenesis with human recombinant VEGF-C FASEB JOURNAL Szuba, A., Skobe, M., Karkkainen, M. J., Shin, W. S., Beynet, D. P., Rockson, N. B., Dakhil, N., Spilman, S., Goris, M. L., Strauss, H. W., Quertermous, T., Alitalo, K., Rockson, S. G. 2002; 16 (12): 1985-?
  • In vivo Imaging of acute cardiac rejection in human patients using (99m)Technetium labeled annexin V AMERICAN JOURNAL OF TRANSPLANTATION Kown, M. H., Strauss, H. W., Blankenberg, F. G., Berry, G. J., Stafford-Cecil, S., Tait, J. F., Goris, M. L., Robbins, R. C. 2001; 1 (3): 270-277

    Abstract

    Annexin V binds phosphatidylserine moieties on apoptotic cells. This study reports the initial experience at Stanford University Medical Center with 99mTc-labeled annexin V imaging as a noninvasive measure of apoptosis in acute cardiac rejection. Ten cardiac transplant patients had 99mTc Annexin V imaging and endomyocardial biopsy (EMB) performed within 24 h. No complications related to 99mTc annexin V administration occurred. Eight patients had ISHLT grade of acute rejection of 1A or less. Five patients had two or more areas of uptake noted in the right ventricle on imaging studies. Two of these patients had positive biopsies: one patient had grade 2 rejection with two focal uptake areas and another had grade 3A rejection with three foci. An additional five patients had either one or zero hot spot areas and corresponding negative EMBs. 99mTc-annexin V appears to be well tolerated and may identify patients with acute cardiac rejection.

    View details for Web of Science ID 000173466800011

    View details for PubMedID 12102261

  • Phase II trial of yttrium-90-DOTA-biotin pretargeted by NR-LU-10 antibody/streptavidin in patients with metastatic colon cancer CLINICAL CANCER RESEARCH Knox, S. J., Goris, M. L., Tempero, M., Weiden, P. L., Gentner, L., Breitz, H., ADAMS, G. P., Axworthy, D., Gaffigan, S., Bryan, K., Fisher, D. R., Colcher, D., Horak, I. D., Weiner, L. M. 2000; 6 (2): 406-414

    Abstract

    A Phase II study of yttrium-90-tetra-azacyclododecanetetra-acetic acid-biotin (90Y-DOTA-biotin) pretargeted by NR-LU-10 antibody/streptavidin (SA) was performed. The primary objectives of the study were to evaluate the efficacy and safety of this therapy in patients with metastatic colon cancer. Twenty-five patients were treated with a single dose of 110 mCi/m2 (mean administered dose, 106.5 +/- 10.3 mCi/m2) of 90Y-DOTA-biotin. There were three components of the therapy. Patients first received NR-LU-10/SA on day 1. A clearing agent (biotin-galactose-human serum albumin) was administered approximately 48 h after the NR-LU-10/SA to remove residual circulating unbound NR-LU-10/SA. Lastly, 24 h after administration of clearing agent, patients received biotin-DOTA-labeled with 110 mCi/m2 90Y. All three components of the therapy were administered i.v. Both hematological and nonhematological toxicities were observed. Diarrhea was the most frequent grade 4 nonhematological toxicity (16%; with 16% grade 3 diarrhea). Hematological toxicity was less severe with 8% grade 3 and 8% grade 4 neutropenia and 8% grade 3 and 16% grade 4 thrombocytopenia. The overall response rate was 8%. Two partial responders had freedom from progression of 16 weeks. Four patients (16%) had stable disease with freedom from progression of 10-20 weeks. Despite the relatively disappointing results of this study in terms of therapeutic efficacy and toxicity, proof of principle was obtained for the pretargeting approach. In addition, valuable new information was obtained about normal tissue tolerance to low-dose-rate irradiation that will help to provide useful guidelines for future study designs.

    View details for Web of Science ID 000085502600013

    View details for PubMedID 10690517

  • Three-Dimensional Quantitative Analysis of Scintigraphic Tomographic Images after Elastic Transformation to a Template. Surgical technology international Goris, M. L., Maclean, M., Pace, W. M., Yee, A., Kwan, A. 2000; IX: 81-90

    Abstract

    The diagnostic information in scintigraphic images is generally not contained in specific morphological image attributes, but in the regional distribution of count rate densities across the organ volumes. In a subclass of scintigraphic images, the evaluation is actually based on a dual comparison.

    View details for PubMedID 12219283

  • [Preliminary evaluation of the effect of an attenuation correction method in myocardial perfusion SPECT]. Revista española de medicina nuclear Cortés-Blanco, A., Fujii, C., Goris, M. L. 1999; 18 (6): 416-424

    Abstract

    We propose a method to assess an attenuation correction method in myocardial perfusion SPECT. Three types of images are obtained: one resulting from a classic acquisition and filtered back-projection (classic), and those resulting from acquisition with a transmission source and an iterative reconstruction, with (music) or without (hybrid) the attenuation correction factored in to compare the three types of images and classify them as normal or abnormal, a three dimensional inter-patient quantitative comparison method was used. Differences were computed as fractions of the myocardial volume in which density differences are significant by population standards. In 7 cases the cumulative difference between prone and supine in hybrid images was 124 and 45 in music images. In 10 cases the cumulative difference between classic vs music images was 279, and between classic and hybrid 86. The AC changed 4/12 cases from abnormal to normal. The attenuation correction effect was concentrated on the septal and inferior walls, but neither exclusively nor evenly among patients. The attenuation correction effectively minimizes attenuation effects by a factor of 2.7, due to a correction of at least 69%. The correction has a small but substantial effect on the results.

    View details for PubMedID 10611567

  • Factors affecting and computation of myocardial perfusion reference images NUCLEAR MEDICINE COMMUNICATIONS Goris, M. L., Hotz, B., Thirion, J. P., Similon, P. 1999; 20 (7): 627-635

    Abstract

    Many quantitative analysis methods for myocardial perfusion studies require as a central step a comparison with a 'normal' or average density distribution map or reference image. It has been recognized, however, that the normal distribution can be affected by patient attributes, including sex and weight or body habitus, and by acquisition attributes, including the choice of tracer and the position of the patient during imaging. Some authors have proposed separate reference images for the sexes and the tracer. This approach fails if a large number of binary attributes have to be considered, since one would need 2" reference images for each attribute. The problem is compounded when continuous attributes (e.g. age and weight) are included, especially if the approach is to average separate homogeneous groups for each attribute. We propose to create case-specific reference images for the interpretation of myocardial perfusion studies by creating a model based on the influence of each attribute. From a non-homogeneous population of normal cases, or cases presumed to be normal on the basis of the Diamond and Forrester stratification, the effect of patient and study attributes on the density distribution in the stress image and the density differences between rest and stress images were computed. The effects are computed by multi-linear regression, to account for cross-correlation. Significance is assigned on the basis of a partial Fisher test. The data are myocardial perfusion images matched in 3D to a template by an elastic transformation. Even though there was some cross-correlation in the data, we were able to show independent effects of sex, position (prone or supine), age, weight, tracer combination and stress method (exercise, persantine and adenosine). Taken as a whole, the multi-linear regression demonstrated a significant effect in 72% of the pixels within the myocardial volume. In addition, the distribution predicted by the model was equivalent to average images from homogeneous matched groups. In conclusion, our approach makes it possible to produce case-specific reference images without the need for multiple homogeneous large groups to produce averages for each possible patient or study attribute.

    View details for Web of Science ID 000081454700006

    View details for PubMedID 10423765

  • Pulmonary SPECT imaging and the stripe sign JOURNAL OF NUCLEAR MEDICINE Pace, W. M., Goris, M. L. 1998; 39 (4): 721-723

    Abstract

    A patient with high clinical suspicion for pulmonary embolism underwent a diagnostic scintigraphic ventilation/perfusion scan. The planar images revealed an unmatched perfusion defect with a stripe sign in the right middle lobe. A stripe sign is the appearance of normally perfused tissue between the defect and the pleural surface suggesting a nonpleural-based abnormality. SPECT images acquired in the same study period, however, failed to demonstrate normally perfused tissue between the defect and the pleural surface. Previous studies have compared planar ventilation/perfusion studies with stripe sign perfusion defects to pulmonary angiography. The results suggest that stripe sign perfusion defects are generally not due to emboli. However, planar imaging is projectional and may miss pleural contact in some perfusion lesions depending on the projection. In the absence of SPECT data, the significance of the stripe sign may need to be reassessed.

    View details for Web of Science ID 000072956600040

    View details for PubMedID 9544688

  • MRI of pulmonary embolism using Gd-DTPA-polyethylene glycol polymer enhanced 3D fast gradient echo technique in a canine model MAGNETIC RESONANCE IMAGING Li, K. C., Pelc, L. R., NAPEL, S. A., Goris, M. L., Lin, D. T., SONG, C. K., Leung, A. N., Rubin, G. D., HOLLETT, M. D., Harris, D. P. 1997; 15 (5): 543-550

    Abstract

    This study was to evaluate the accuracy of MR angiography (MRA) using a Gd-DTPA-polyethylene glycol polymer (Gd-DTPA-PEG) with a 3D fast gradient echo (3D fgre) technique in diagnosing pulmonary embolism in a canine model. Pulmonary emboli were created in six mongrel dogs (20-30 kg) by injecting tantalum oxide-doped autologous blood clots into the femoral veins via cutdowns. MRI was performed with a 1.5 T GE Signa imager using a 3D fgre sequence (11.9/2.3/15 degrees) following intravenous injection of 0.06 mmol Gd/kg of Gd-DTPA-PEG. The dogs were euthanized and spiral CT of the lungs were then obtained on the deceased dogs. The MRI images were reviewed independently and receiver-operating-characteristic (ROC) curves were used for statistical analysis using spiral CT results as the gold standard. The pulmonary emboli were well visualized on spiral CT. Out of 108 pulmonary segments in the six dogs, 24 contained emboli >2 mm and 27 contained emboli < or = 2 mm. With unblinded review, MRI detected 79% of emboli >2 mm and only 48% of emboli < or = 2 mm. The blinded review results were significantly worse. Gd-DTPA-PEG enhanced 3D fgre MRI is potentially able to demonstrate pulmonary embolism with fairly high degree of accuracy, but specialized training for the interpretations will be required.

    View details for Web of Science ID A1997XM76800004

    View details for PubMedID 9253998

  • Yttrium-90-labeled anti-CD20 monoclonal antibody therapy of recurrent B-cell lymphoma CLINICAL CANCER RESEARCH Knox, S. J., Goris, M. L., Trisler, K., Negrin, R., Davis, T., Liles, T. M., GRILLOLOPEZ, A., Chinn, P., Varns, C., Ning, S. C., Fowler, S., Deb, N., Becker, M., Marquez, C., Levy, R. 1996; 2 (3): 457-470

    Abstract

    A Phase I/II dose escalation study of 90Y-murine anti-CD20 monoclonal antibody (mAb) in patients with recurrent B-cell lymphoma was performed. The primary objectives of the study were: (a) to determine the effect of the preinfusion of unlabeled anti-CD20 mAb on the biodistribution of 111In-anti-CD20 mAb; (b) to determine the maximal tolerated dose of 90Y-anti-CD20 mAb that does not require bone marrow transplantation; and (c) to evaluate the safety and antitumor effect of 90Y-anti-CD20 mAb in patients with recurrent B-cell lymphoma. Eighteen patients with relapsed low- or intermediate-grade non-Hodgkin's lymphoma were treated. Biodistribution studies with 111In-anti-CD20 mAb were performed prior to therapy. Groups of three or four patients were treated at dose levels of approximately 13.5, 20, 30, 40, and 50 mCi 90Y-anti-CD20 mAb. Three patients were retreated at the 40-mCi dose level. The use of unlabeled antibody affected the biodistribution favorably. Nonhematological toxicity was minimal. The only significant toxicity was myelosuppression. The overall response rate following a single dose of 90Y-anti-CD20 mAb therapy was 72%, with six complete responses and seven partial responses and freedom from progression of 3-29+ months following treatment. Radioimmunotherapy with

    View details for Web of Science ID A1996TY62000004

    View details for PubMedID 9816191

  • THE HYPOXIC CYTOTOXIN SR-4233 INCREASES THE EFFECTIVENESS OF RADIOIMMUNOTHERAPY IN MICE WITH HUMAN NON-HODGKINS-LYMPHOMA XENOGRAFTS INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Wilder, R. B., McGann, J. K., SUTHERLAND, W. R., Waller, E. K., Minchinton, A. I., Goris, M. L., Knox, S. J. 1994; 28 (1): 119-126

    Abstract

    To determine if either the hypoxic cell radiosensitizer etanidazole (SR 2508) or the hypoxic cytotoxin SR 4233 could improve the effectiveness of radioimmunotherapy.LC4 (an IgG1 monoclonal antibody directed toward malignant T cells) and MB-1 (an irrelevant isotype-matched control antibody) were injected intraperitoneally into severe combined immunodeficient phenotype mice with human cutaneous T cell lymphoma xenografts in order to determine the distribution of the antibodies in the tumors and normal tissues as a function of time. Computerized-pO2-histography was used to measure the median oxygen tension in the tumors. Tumor-bearing mice were treated with: (a) LC4; (b) 90Y-LC4; (c) 90Y-MB-1; (d) whole body irradiation delivered via an external 137Cs source; (e) etanidazole and 90Y-LC4; (f) SR 4233 and 90Y-LC4; (g) etanidazole; and (h) SR 4233. An additional group of mice received no treatment and served as controls. A tumor growth delay assay was used to assess the effectiveness of the different treatment regimens.LC4 accumulated in the tumors to a significantly greater extent than MB-1 (p < 0.001) and reached a peak concentration in the tumors 5 days post-injection. The human cutaneous T cell lymphoma xenografts had a relatively low median oxygen tension. LC4 by itself was able to produce a minor decrease in tumor size (control vs. LC4; p = 0.001). 90Y-LC4 produced greater tumor growth delay than LC4 alone (LC4 vs. 90Y-LC4; p = 0.01); however, the Yttrium-90 caused neutropenia and weight loss. The 90Y-labeled tumor-specific and non-specific antibodies both exerted greater tumor growth delay than externally delivered whole body irradiation (p < or = 0.03) due to preferential uptake of the antibodies in the tumors. Etanidazole and SR 4233 by themselves did not significantly inhibit the growth of the tumors. Etanidazole did not significantly enhance the tumor growth delay produced by 90Y-LC4 (90Y-LC4 vs etanidazole and 90Y-LC4, p = 0.13). SR 4233, on the other hand, did enhance the tumor growth delay produced by 90Y-LC4 (90Y-LC4 vs. SR 4233 and 90Y-LC4, p = 0.046). The neutropenia and weight loss caused by 90Y-LC4 were exacerbated slightly (< 10%) by the administration of SR 4233.A first generation hypoxic cytotoxin, SR 4233, was able to enhance the tumor growth delay produced by radioimmunotherapy in severe combined immunodeficient phenotype mice with human cutaneous T cell lymphoma xenografts.

    View details for Web of Science ID A1994MP35300016

    View details for PubMedID 8270432

  • MODELING THE INTEGRATION OF MYOCARDIAL REGIONAL PERFUSION AND FUNCTION NUCLEAR MEDICINE COMMUNICATIONS Goris, M. L., Thompson, C., Malone, L. J., Franken, P. R. 1994; 15 (1): 9-20

    Abstract

    The purpose of the study is to describe a method for the investigation of myocardial kinetics (wall motion or wall thickening) to define myocardial perfusion characteristics further. The data are myocardial perfusion single photon emission computed tomographic images gated in eight time bins, following the administration of a 99Tcm-labelled perfusion agent. Wall motion is defined by the phase and amplitude of the centripetal motion of the first moment of the myocardial count rate density distribution along a radius originating in the centre of the left ventricular cavity. Wall thickening is defined by phase and amplitude of the changes in the second moment of the density distribution along the radius multiplied by the maximum density. Wall motion amplitude was abnormal in 28% of transient and 43% of fixed perfusion abnormalities, phase delays were present in 28 and 57%, respectively. Wall thickening was abnormal in amplitude in 14% of transient and 86% of fixed perfusion abnormalities. We conclude that the positive predictive value of wall-thickening abnormalities relative to fixed perfusion abnormalities is high (86%). Whether fixed perfusion defects with normal wall thickening represent viable myocardium remains to be investigated.

    View details for Web of Science ID A1994MZ73100003

    View details for PubMedID 8152699

  • LOCAL HYPERTHERMIA AND SR-4233 ENHANCE THE ANTITUMOR EFFECTS OF RADIOIMMUNOTHERAPY IN NUDE-MICE WITH HUMAN COLONIC ADENOCARCINOMA XENOGRAFTS CANCER RESEARCH Wilder, R. B., Langmuir, V. K., Mendonca, H. L., Goris, M. L., Knox, S. J. 1993; 53 (13): 3022-3027

    Abstract

    Local hyperthermia and the hypoxic cytotoxin SR 4233 were administered to nude mice with 693 +/- 47 mm3 (mean +/- SE) s.c. HCT-8 human colonic adenocarcinoma xenografts in an attempt to enhance the antitumor effects of radioimmunotherapy. Biodistribution studies revealed preferential binding of NR-Lu-10, a murine monoclonal antibody, to the tumors compared with an isotype-matched control antibody, CCOO16-3.A single injection of 25 microCi 90Y-NR-Lu-10 significantly inhibited tumor growth (control versus 90Y-NR-Lu-10: P = 0.048). The administration of hyperthermia at 41.5 degrees C for 1 h immediately following the injection of 111In-labeled NR-Lu-10 up-regulated tumor-associated antigen expression and increased antibody uptake in the tumors by 73% (P = 0.001) without significantly affecting antibody uptake in normal tissues. However, the heat treatment did not produce a more homogeneous distribution of the antibodies in the tumors and did not significantly enhance the tumor growth delay produced by 90Y-NR-Lu-10 (P = 0.07). The administration of local hyperthermia at 43.0 degrees C for 1 h, on the other hand, had direct cytotoxic effects (P = 0.03) and enhanced the tumor growth delay produced by 90Y-NR-Lu-10 (P = 0.01). SR 4233 also enhanced the tumor growth delay produced by 90Y-NR-Lu-10 (P = 0.03). The greatest antitumor effects were observed when both hyperthermia at 43.0 degrees C and SR 4233 were administered in combination with 90Y-NR-Lu-10 (P = 0.002). No toxicity was produced by the local hyperthermia, and the only toxicities produced by 90Y-NR-Lu-10 and SR 4233 were neutropenia and weight loss.

    View details for Web of Science ID A1993LL13100018

    View details for PubMedID 8319209

  • CORRELATION OF TUMOR SENSITIVITY TO LOW-DOSE-RATE IRRADIATION WITH G2/M-PHASE BLOCK AND OTHER RADIOBIOLOGICAL PARAMETERS RADIATION RESEARCH Knox, S. J., Sutherland, W., Goris, M. L. 1993; 135 (1): 24-31

    Abstract

    The efficacy of exponentially decreasing low-dose-rate irradiation was compared with that of equivalent doses of multiply fractionated high-dose-rate external-beam irradiation in mice with three different kinds of tumors that varied in terms of alpha/beta ratio, tumor volume doubling times, and cell cycle times. Cell cycle distribution was measured after low-dose-rate and high-dose-rate irradiation. The relative efficacy of low-dose-rate irradiation versus equivalent doses of high-dose-rate irradiation was correlated with the extent of arrest of cells in G2 phase of the cell cycle. Unlike 38C13 murine B-cell lymphoma, neither the HT29 human colorectal xenograft or the SNB75 human glioblastoma xenograft was significantly more sensitive to low-dose-rate than fractionated high-dose-rate irradiation. The 38C13 B-cell lymphoma also had the shortest tumor volume doubling and cell cycle times, the most G2 arrest after low-dose-rate irradiation, more G2 arrest with low-dose-rate than high-dose-rate irradiation, and the highest alpha/beta ratio. The data presented here support the hypothesis that dose-rate effects may be minimal for tumors with small shoulders and large alpha/beta ratios and that arrest of cells in G2 phase plays an important role in cell death mediated by low-dose-rate irradiation. The proliferative rates of tumor cells may modify dose-rate effects further, and the interaction of all of these factors may explain in part the increased efficacy of low-dose-rate irradiation and radioimmunotherapy compared with high-dose-rate irradiation that has been reported in some animal models.

    View details for Web of Science ID A1993LM85600003

    View details for PubMedID 8327657

  • THE EFFECT OF UNLABELED MONOCLONAL-ANTIBODY (MAB) ON THE BIODISTRIBUTION OF I-131 ANTIIDIOTYPE MAB IN MURINE B-CELL LYMPHOMA RADIOTHERAPY AND ONCOLOGY Schiele, J., Knox, S. J., RUEHL, W., Goris, M. L. 1992; 24 (3): 169-176

    Abstract

    The 38C13 murine B cell lymphoma model was used to study the effect of the preinjection of unlabelled anti-idiotype monoclonal antibody (mAb) on the subsequent biodistribution of 131I-anti-idiotype mAb. Mice with established tumors received 0-500 micrograms of unlabelled anti-idiotype mAb 24 h prior to the administration of 131I-anti-idiotype (specific), or both 125I-anti-idiotype and 131I-isotype-matched irrelevant control (nonspecific) mAb. Mice were counted daily in a gamma counter and sacrificed at 2-144 h following injection. Mice were dissected and the weight and activity of the animals and organs were measured. Mice were bled periodically and circulating idiotype levels were measured using an ELISA assay. Five hundred micrograms of unlabelled anti-idiotype mAb increased the retention time of the specific but not the nonspecific mAb in all organs and tumor. Following pretreatment with unlabelled mAb, the cumulative tumor/whole body and tumor/normal organ ratios became similar to those of the nonspecific mAb, with concentration ratios (specific/nonspecific mAb) of approximately 1, which persisted until 96 h post injection when circulating idiotype reappears in antigen excess. In the absence of unlabelled mAb there was less retention in tumor and normal tissue. This is presumed to be due in part to decreased levels of circulating 131I-mAb secondary to rapid plasma clearance of antigen-antibody complexes and tumor cell mediated dehalogenation, which results when the specific mAb specifically binds the targeted antigen. Thus, the addition of unlabelled mAb increased the retention by decreasing the specific behavior of the anti-idiotypic antibody.

    View details for Web of Science ID A1992JL59000005

    View details for PubMedID 1410571

  • OVERVIEW OF ANIMAL STUDIES COMPARING RADIOIMMUNOTHERAPY WITH DOSE EQUIVALENT EXTERNAL BEAM IRRADIATION RADIOTHERAPY AND ONCOLOGY Knox, S. J., Goris, M. L., Wessels, B. W. 1992; 23 (2): 111-117

    Abstract

    As the field of radioimmunotherapy (RIT) continues to develop and looks increasingly promising, there is growing interest in the radiobiology of RIT. Recently, several investigators have conducted studies in animal models comparing the relative efficacy of RIT with dose equivalent external beam irradiation. Although these studies are the first of many to follow, the results are provocative and several patterns are suggested by the available data. The results of the studies are summarized and compared, and preliminary hypotheses that might explain the reported observations are discussed. In summary, results from studies comparing the efficacy of RIT with external beam irradiation have been variable and may be indicative of different underlying mechanisms. While the particular experimental model, design and methodology used to compare the efficacy of RIT with external beam irradiation are probably important influences upon subsequent observations, it appears that for a given tumor type, the size of the survival curve shoulder or alpha/beta ratio, and tumor doubling time are important determinants of the magnitude of the dose rate effect. When this effect is minimal, it is possible that other factors such as reoxygenation, the arrest of cells in G2, and selective targeting of tumor by radiolabelled antibody may explain, in part, the increased efficacy of RIT compared with external beam irradiation that has been observed in some systems.

    View details for Web of Science ID A1992HJ27900007

    View details for PubMedID 1546186

  • Case report: diffuse gastrointestinal bleeding. American journal of physiologic imaging Goris, M. L., Licho, R. 1992; 7 (1): 42-43

    Abstract

    Diffuse gastrointestinal bleeding in an immunodeficient patient is presented. Two hours after in vivo erythrocyte labeling, abnormal activity was observed in the wall of a distended colon. If this abnormal concentration had been luminal, a focal, surgically treatable lesion could not have been excluded. This pattern of hemorrhagic colonic lesions has been described pathologically, but not scintigraphically, in immune deficient patients.

    View details for PubMedID 1325815

  • THE BIODISTRIBUTION OF IN-111 ANTI-BFGF IN A VARIETY OF TUMORS - CORRELATION WITH CELL-BINDING ASSAYS ANNALS OF THE NEW YORK ACADEMY OF SCIENCES Knox, S. J., Brown, J. M., McGann, J., Sutherland, W., Goris, M. L., Herblin, W. F., Gross, J. L. 1991; 638: 497-502

    View details for Web of Science ID A1991JM20900072

    View details for PubMedID 1785829

  • LONG-TERM SCINTIGRAPHIC APPEARANCE OF EXTREMITIES FOLLOWING BONE-TUMOR RESECTION AND ALLOGRAFT RECONSTRUCTION CLINICAL NUCLEAR MEDICINE SMITH, J. T., Smith, L. M., Rinsky, L., Goris, M. L. 1991; 16 (12): 907-909

    Abstract

    The authors retrospectively reviewed the Tc-99m medronate scan findings in six patients who had no evidence of metastatic disease following en bloc resection of a primary osteosarcoma and subsequent limb reconstruction using allograft bone. Persistently increased radionuclide uptake was noted at the junction between the host bone and the graft, while the graft cortical bone showed persistently decreased activity. Radionuclide uptake at the periphery of the graft varied. Over time the youngest patient in the series had increasingly normal scan findings.

    View details for Web of Science ID A1991KC60900005

    View details for PubMedID 1663013

  • PARATHYROID IMAGING JOURNAL OF NUCLEAR MEDICINE Goris, M. L., Basso, L. V., Keeling, C. 1991; 32 (5): 887-889

    View details for Web of Science ID A1991FL18300037

    View details for PubMedID 1827150

  • DETERMINANTS OF THE ANTITUMOR EFFECT OF RADIOLABELED MONOCLONAL-ANTIBODIES CANCER RESEARCH Knox, S. J., Levy, R., MILLER, R. A., UHLAND, W., Schiele, J., RUEHL, W., FINSTON, R., DAYLOLLINI, P., Goris, M. L. 1990; 50 (16): 4935-4940

    Abstract

    The murine B-cell lymphoma 38C13 model was used to study the radiobiological effect of 131I-monoclonal antibody (MAB) therapy compared with dose equivalent external beam irradiation. Continuous exponentially decreasing low dose rate (LDR) gamma-irradiation, and multiply fractionated (MF) X-irradiation were compared with dose equivalent 131I-MAB. The relative therapeutic efficacy of radioimmunotherapy, and the relative contribution of (a) low dose rate; (b) whole body irradiation; and (c) microdosimetry to the overall effect were determined. Groups of mice with or without B-cell lymphoma were treated with either (a) 131I-anti-idiotype MAB; (b) 131I-isotype-matched irrelevant control MAB; (c) 5-15 Gy 250 kV X-irradiation given as a single fraction; (d) 2.5-30 Gy 250 kV X-irradiation given in 10 fractions/2 weeks; or by (e) continuous exponentially decreasing gamma-irradiation via a 137Cs source, which simulated the effective t1/2 of the 131I-MAB. In tumor-free mice the LD50/30 was approximately 10 Gy for MF and LDR external irradiation, and 11-12 Gy for 131I-MAB. However, the effect of these modes of irradiation on tumor size differed significantly. The cumulative percentage of tumor reduction averaged over 12 days was 0.635 +/- 0.055%/Gy for MF, and 1.36 +/- 0.061%/Gy for LDR external irradiation (a relative efficacy factor of 1.63 for LDR irradiation; P = 0.01). Assuming homogeneous body distribution, the tumor reduction effect over 12 days for 131I-MAB was 2.064 +/- 0.133%/Gy for specific, and 1.742 +/- 0.1%/Gy for nonspecific isotype-matched irrelevant 131I-MAB (P = 0.02). When 131I-MAB was compared to LDR external irradiation, the relative efficacy factor was 1.99 (P less than 0.001). In summary, there was a dose rate effect on tumor response, which may in part explain the efficacy of radioimmunotherapy. The additional effect of 131I-MAB on tumor response was only partially explained by the cumulative concentration ratio of 131I-MAB tumor/131I-MAB whole body, which was on average 1.7. This relatively low concentration ratio was partly due to tumor-mediated dehalogenation. Thus, the overall tumor response was a function of the total dose, dose rate, and both the specific and nonspecific distribution of 131I-MAB.

    View details for Web of Science ID A1990DT62000020

    View details for PubMedID 2379158

  • Validation of diagnostic procedures on stratified populations: application on the quantification of thallium myocardial perfusion scintigraphy. American journal of physiologic imaging Goris, M. L., BRETILLE, J., Askienazy, S., Purcell, G. P., Savelli, V. 1989; 4 (1): 11-15

    Abstract

    In this report we present a method for the quantitative description of the degree of deviation from the norm of 201thallium single photon emission tomographic (SPECT) data. Validation is obtained from the frequency of "positive" outcomes in subgroup of patients in whom the prevalence of coronary artery disease, for the group as a whole, is known, even if individual patient outcomes are not verified. This approach overcomes the bias associated with nonrandomized clinical studies, in which the likelihood that a more invasive but definitive procedure (coronary arteriogram) will be performed is influenced by the result of the outcome of the procedure under study.

    View details for PubMedID 2647110

  • NONINVASIVE ASSESSMENT OF DONOR AND NATIVE HEART FUNCTION AFTER HETEROTOPIC HEART-TRANSPLANTATION JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Allen, M. D., NAASZ, C. A., Popp, R. L., Hunt, S. A., Goris, M. L., Oyer, P. E., Stinson, E. B. 1988; 95 (1): 75-81

    Abstract

    The contribution of the donor heart to total circulatory performance after heterotopic heart transplantation has been difficult to assess. First-pass nuclear angiocardiography and directional Doppler echocardiography were used to examine separately left and right ventricular function of the donor heart after heterotopic transplantation. A comparison was made between two patients, one with a low initial pulmonary vascular resistance and one with a high, relatively fixed pulmonary vascular resistance. In both cases, currently available noninvasive techniques allowed confirmation of the expectation that the donor left ventricle can function effectively as a left ventricular bypass. In neither case was recovery of the native heart demonstrated. The contribution of the donor right ventricle to total right ventricular output appeared to be dependent on the condition of the donor heart and on the pulmonary vascular resistance. In situations with a high pulmonary vascular resistance and end-stage right ventricular failure, it was concluded that the donor heart may not at first constitute an effective assist for the native right ventricle. Native right ventricular failure may then become a major factor influencing survival after heterotopic heart transplantation.

    View details for Web of Science ID A1988L686700010

    View details for PubMedID 3275840

  • Two-dimensional mapping of three-dimensional SPECT data: a preliminary step to the quantitation of thallium myocardial perfusion single photon emission tomography. American journal of physiologic imaging Goris, M. L., Boudier, S., BRIANDET, P. A. 1987; 2 (4): 176-180

    Abstract

    A method is presented by which tomographic myocardial perfusion data are prepared for quantitative analysis. The method is characterized by an interrogation of the original data, which results in a size and shape normalization. The method is analogous to the circumferential profile methods used in planar scintigraphy but requires a polar-to-cartesian transformation from three to two dimensions. As was the case in the planar situation, centering and reorientation are explicit. The degree of data reduction is evaluated by reconstructing "idealized" three-dimensional data from the two-dimensional sampling vectors. The method differs from previously described approaches by the absence in the resulting vector of a coordinate reflecting cartesian coordinate in the original data (slice number).

    View details for PubMedID 3502531

  • Interrogation and display of single photon emission tomography data as inherently volume data. American journal of physiologic imaging Goris, M. L., Boudier, S., BRIANDET, P. A. 1986; 1 (4): 168-180

    Abstract

    The purpose of single photon emission computed tomography (SPECT) data is to map the tracer concentration from the three-dimensional object into a three-dimensional image array. The conventional interrogation of the data is through slice interrogation. In this paper we explore display methods in which the data are directly interrogated and processed as three-dimensional data. This includes direct addressing of sagittal, transverse, and frontal slices, around a targeted subvolume, and direct addressing of nonorthogonal slices. The three-dimensional aspect of the data is further accommodated by thresholding and edge definition in space. Finally, morphological information, which is sparse in scintigraphic slices, is recaptured by the generation of planar data derived from data processed in the three-dimensional space.

    View details for PubMedID 3502525

  • SKELETAL SCINTIGRAPHY FOR THE DIAGNOSIS OF MALIGNANT METASTATIC DISEASE TO THE BONES RADIOTHERAPY AND ONCOLOGY Goris, M. L., BRETILLE, J. 1985; 3 (4): 319-329

    Abstract

    The use of skeletal scintigraphy for the detection of metastatic disease of the bone is reviewed. The review is based on published data for sensitivity, specificity, yield and prognostic value. The analysis, and interpretation of published data is complicated by the variation in criteria. It appears nonetheless, that for a number of tumors the relative (in comparison with other methods) and absolute (based on outcome prediction) sensitivity is high. For certain tumors in early stages, and in asymptomatic patients the yield (of positive studies) is low, even when the prognostic value is high. Those factors should be weighed with the availability of therapeutic options to determine the clinical efficacy of skeletal scintigraphy.

    View details for Web of Science ID A1985AKR4700005

    View details for PubMedID 3892595

Conference Proceedings


  • Therapeutic lymphangiogenesis in a rabbit ear model of chronic post-surgical lymphatic insufficiency Szuba, A., Skobe, M., Shin, W., Beynet, D. P., Rockson, N. B., Dakhil, N., Goris, M. L., Strauss, H. W., Quertermous, T., Alitalo, K., Rockson, S. G. FEDERATION AMER SOC EXP BIOL. 2002: A516-A516
  • A model for chronic, post-surgical lymphatic insufficiency Shin, W., Szuba, A., Skobe, M., Beynet, D. P., Rockson, N. B., Dakhil, N., Goris, M. L., Strauss, H. W., Quertermous, T., Alitalo, K., Rockson, S. G. FEDERATION AMER SOC EXP BIOL. 2002: A123-A124
  • A model of acute, post-surgical lymphedema Beynet, D. P., Szuba, A., Skobe, M., Rockson, N. B., Dakhil, N., Shin, W., Goris, M. L., Strauss, H. W., Quertermous, T., Alitalo, K., Rockson, S. G. FEDERATION AMER SOC EXP BIOL. 2002: A124-A124
  • ORGAN MODELING IN THE QUANTITATION OF PLANAR IMAGES FOR DISTRIBUTION STUDIES Goris, M. L., Knox, S. A., Nielsen, K. R., BOUILLANT, O. JOHN WILEY & SONS INC. 1994: 919-922

    Abstract

    The advantage of whole-body imaging for distribution studies is that it accounts for all activities. The problem, however, is that the classic approach to determining distribution from planar images does not accommodate overlapping structures. That approach assumes implicitly that the sampling region is a prismoid whose cross-section, parallel to the detector plane, is defined by a region of interest and whose sides are orthogonal to the detector plane.In the proposed organ-model approach, the region of interest is assumed explicitly to be the projected shadow of an organ or structure, whose general shape is known from anatomic generality, and whose size or specific shape variation is defined by the shadow or region of interest. If "j" is a pixel in the organ shadow "i", a fraction "Vij" of the volume of organ "i" is assumed to project orthogonally in "j". More than one organ shadow can overlap, in which case the volumes projecting in "j" are the sum of "Vij" over "i". The activity "Aj" (count rate density) in any location "j" is defined by the linear combination of volumes "Vij" and concentrations "Ci". For all the pixels in the image, this defines an overdetermined set of linear equations that can be solved by matrix inversion for "Ci", the organ concentrations.The organ-model method was tested on simulated and phantom data. It proved, on serial and repeat processing, to be robust (not subject to large errors due to small variations) if the images had sufficient contrast. This method was found to be superior to the classic approach in evaluating the same data, because in the classic approach, the border regions are too heavily weighted, and therefore, the size of the sampling region is critical. Furthermore, the expression of the results in concentrations is more relevant to dosimetry, the derivation of which is based on cumulative concentrations.Modeling organ shadows is a viable improvement on the use of regions of interest to quantify tracer distribution in planar imaging.

    View details for Web of Science ID A1994MV41800025

    View details for PubMedID 8306280

  • THE QUANTIFICATION OF PLANAR SCINTIGRAPHY USING 3-DIMENSIONAL MODELING OF ORGAN SHADOWS Goris, M. L. WILEY-LISS, INC. 1991: 531-539

    Abstract

    A method to define biodistribution from planar scintigraphic data is presented. Sampling regions or regions of interest (ROI's) are first defined as the projection contour of organs. From anatomical knowledge the three dimensional volume of the organ whose shadow has been traced is reconstructed. When the relevant organ volumes including the whole body or relevant whole body part have been defined, the count rate density in each pixel is assumed to represent the sum of the product of the projecting organ partial volumes times the tracer concentrations in the underlying organs. The solution (the definition of organ concentrations) is found by a matrix inversion. Validation is obtained in two ways. The first method is illustrative: an image is reconstructed from the defined volumes modulated by the computed concentrations. This image, if the method is correct, should be a crisp equivalent of the original data and closely similar to it following blurring with a convolution kernel equal to the imaging system's point spread function. The second is analytical: from reconstructed S.P.E.C.T. data in which voxel values are directly proportional to organ concentrations, a planar image is reconstructed. Organ average voxel values are computed in the S.P.E.C.T. image with volumetric ROI's and in the reprojected planar image using the method described here. The methods should yield the same concentration data but for a scaling factor. The method has the advantage that it yields volumetric and concentration data which are directly applicable to MIRD type analysis. In effect, the standard man assumptions in MIRD analysis have been incorporated in the calculation of the concentrations.

    View details for Web of Science ID A1991BS33M00038

    View details for PubMedID 1988999

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