All Publications

  • PSMA-and GRPR-targeted PET: Preliminary Results in Patients with Biochemically Recurrent Prostate Cancer Baratto, L., Duan, H., Hatami, N., Song, H., Davidzon, G., Franc, B., Aparici, C., Moradi, F., Nguyen, J., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2020
  • A pilot study of F-18-FSPG SiPM-based PET/CT in patients referred for exclusion of active cardiac sarcoidosis and negative or non-diagnostic F-18-FDG PET/CT Duan, H., Hatami, N., Baratto, L., Davidzon, G., Aparici, C., Gambhir, S., Koglin, N., Witteles, R., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2020
  • Ga-68-RM2 PET/CT in Patients with Newly Diagnosed Intermediate- or High-Risk Prostate Cancer Baratto, L., Duan, H., Hatami, N., Aparici, C., Davidzon, G., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2020
  • Determining optimal uptake time for Ga-68-labeled radiopharmaceuticals targeting gastrin-releasing peptide receptors with a modified NEMA phantom. Ramos, K., Ferri, V., Baratto, L., Duan, H., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2020
  • Ga-68-PSMA-11 PET/MR Imaging before prostatectomy: correlation with surgical pathology and two-year follow up Moradi, F., Baratto, L., Duan, H., Hatami, N., Davidzon, G., Sonn, G., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2020
  • Response to: Letter to the Editors: Re: Simultaneous PET/MRI in the Evaluation of Breast and Prostate Cancer Using Combined Na[18F]F and [18F]FDG: A Focus on Skeletal Lesions. Molecular imaging and biology Sonni, I., Minamimoto, R., Baratto, L., Iagaru, A. 2020

    View details for DOI 10.1007/s11307-020-01471-2

    View details for PubMedID 31933023

  • Imaging the Distribution of Gastrin Releasing Peptide Receptors in Cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Baratto, L., Duan, H., Maecke, H. R., Iagaru, A. 2020


    Targeting tumor-expressed receptors using selective molecules for diagnostic, therapeutic or both diagnostic and therapeutic (theragnostic) purposes is a promising approach in oncological applications. Such approaches have increased significantly over the past decade. Peptides such as gastrin-releasing peptide receptors (GRPR) targeting radiopharmaceuticals are small molecules with fast blood clearance and urinary excretion. They demonstrate good tissue diffusion, low immunogenicity, and highly selective binding to their target cell-surface receptors. They are also easily produced. GRPR, part of the bombesin (BBN) family, are overexpressed in many tumors, including breast and prostate cancer, and therefore represent an attractive target for future development.

    View details for DOI 10.2967/jnumed.119.234971

    View details for PubMedID 32060215

  • The Effect of Various ? Values on Image Quality and Semiquantitative Measurements in 68Ga-RM2 and 68Ga-PSMA-11 PET/MRI Images Reconstructed With a Block Sequential Regularized Expectation Maximization Algorithm. Clinical nuclear medicine Baratto, L., Duan, H., Ferri, V., Khalighi, M., Iagaru, A. 2020


    To compare the block sequential regularized expectation maximization (BSREM) algorithm with the ordered subsets expectation maximization (OSEM) algorithm and to evaluate how different penalty factors (b values) influence image quality and SUV measurements.We analyzed data from 78 prostate cancer patients who underwent Ga-RM2 (n = 42) or Ga-prostate-specific membrane antigen (PSMA)-11 (n = 36) PET/MRI. The raw PET data were retrospectively reconstructed using both time-of-flight (TOF)-BSREM with b values of 250, 350, 500, 750, and 1000 and TOF-OSEM. Each reconstruction was reviewed independently by 3 nuclear medicine physicians and scored qualitatively using a Likert scale (1 = poor, 5 = excellent quality). SUV measurements were analyzed as well.Fifty-seven lesions were detected (21 on Ga-RM2 and 36 on Ga-PSMA-11 PET/MRI); SUVmax decreased with the increase of ? values for both tracers. Background noise (SUVsd) decreased with increasing of ? values for both tracers. The mean SD scores for Ga-RM2 PET images were 2.4 0.5 for b = 250 reconstructions, 3.2 0.6 for b = 350, 4 0.6 for b = 500, 4.5 0.5 for b = 750, 4.4 0.7 for b = 1000, and 3.4 0.6 for TOF-OSEM. The mean SD scores for Ga-PSMA-11 PET images were 3.2 0.8 for b = 250 reconstructions, 4.1 0.8 for b = 350, 4.7 0.6 for b = 500, 4.8 0.4 for b = 750, 4.7 0.6 for b = 1000, and 3.8 0.5 for TOF-OSEM.Time-of-flight-BSREM algorithm improves image quality. Different b values should be used for different Ga-labeled radiopharmaceuticals such as those targeting GRPR and PSMA receptors. Once selected, the same b value should be consistently used because SUVmax measurements differ with different b values.

    View details for DOI 10.1097/RLU.0000000000003075

    View details for PubMedID 32433170

  • Evaluation of integrin alphavbeta6 cystine knot PET tracers to detect cancer and idiopathic pulmonary fibrosis. Nature communications Kimura, R. H., Wang, L., Shen, B., Huo, L., Tummers, W., Filipp, F. V., Guo, H. H., Haywood, T., Abou-Elkacem, L., Baratto, L., Habte, F., Devulapally, R., Witney, T. H., Cheng, Y., Tikole, S., Chakraborti, S., Nix, J., Bonagura, C. A., Hatami, N., Mooney, J. J., Desai, T., Turner, S., Gaster, R. S., Otte, A., Visser, B. C., Poultsides, G. A., Norton, J., Park, W., Stolowitz, M., Lau, K., Yang, E., Natarajan, A., Ilovich, O., Srinivas, S., Srinivasan, A., Paulmurugan, R., Willmann, J., Chin, F. T., Cheng, Z., Iagaru, A., Li, F., Gambhir, S. S. 2019; 10 (1): 4673


    Advances in precision molecular imaging promise to transform our ability to detect, diagnose and treat disease. Here, we describe the engineering and validation of a new cystine knot peptide (knottin) that selectively recognizes human integrin alphavbeta6 with single-digit nanomolar affinity. We solve its 3D structure by NMR and x-ray crystallography and validate leads with 3 different radiolabels in pre-clinical models of cancer. We evaluate the lead tracer's safety, biodistribution and pharmacokinetics in healthy human volunteers, and show its ability to detect multiple cancers (pancreatic, cervical and lung) in patients at two study locations. Additionally, we demonstrate that the knottin PET tracers can also detect fibrotic lung disease in idiopathic pulmonary fibrosis patients. Our results indicate that these cystine knot PET tracers may have potential utility in multiple disease states that are associated with upregulation of integrin alphavbeta6.

    View details for DOI 10.1038/s41467-019-11863-w

    View details for PubMedID 31611594

  • Malignant cutaneous melanoma:updates inPET imaging. Current radiopharmaceuticals Laudicella, R., Baratto, L., Minutoli, F., Baldari, S., Iagaru, A. 2019


    BACKGROUND: Cutaneous malignant melanoma is a neoplasm whose incidence and mortality are dramatically increasing. 18F-FDG PET/CT gained clinical acceptance over the past 2 decades in the evaluation of several glucose-avid neoplasms, including malignant melanoma, particularly for the assessment for distant metastases, recurrence and response to therapy.OBJECTIVE: To describe the advancements of nuclear medicine for imaging melanoma with particular attention to 18F-FDG-PET, and its current state-of-the-art technical innovations.METHODS: A comprehensive search strategy was used based on SCOPUS and PubMed databases. From all studies published in English, we selected the articles that evaluated the technological insights of 18F-FDG-PET in the assessment of melanoma.RESULTS: State-of-the-art silicon photomultipliers based detectors ("digital") PET/CT scanners are nowadays more common, showing technical innovations that may have beneficial implications for patients with melanoma. Steady improvements in detectors design and architecture, as well as the implementation of both software and hardware technology (i.e., TOF, point spread function, etc.), resulted in significant improvements in PET image quality while reducing radiotracer dose and scanning time.CONCLUSION: Recently introduced digital PET detector technology in PET/CT and PET/MRI yields higher intrinsic system sensitivity compared with the latest generation analog technology, enabling the detection of very small lesions with potential impact on disease outcome.

    View details for DOI 10.2174/1874471012666191015095550

    View details for PubMedID 31749439

  • Physiological 68Ga-RM2 uptake in patients with biochemically recurrent prostate cancer: an atlas of semi-quantitative measurements. European journal of nuclear medicine and molecular imaging Baratto, L., Duan, H., Laudicella, R., Toriihara, A., Hatami, N., Ferri, V., Iagaru, A. 2019


    AIM: 68Ga-RM2 is a bombesin (BBN) analog that targets the gastrin releasing peptide receptors (GRPR) overexpressed in many cancer cells, including prostate cancer (PC). It has been reported to successfully detect primary and recurrent PC. Here, we describe the distribution and range of physiological uptake of 68Ga-RM2 in 95 patients with biochemically recurrent (BCR) PC.MATERIALS AND METHODS: Ninety-five participants had simultaneous PET/MRI for BCR PC and were prospectively enrolled in this study. Maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean) were measured in 24 normal anatomical structures for each participant. Three readers evaluated the images independently. Uptake in various normal tissues was classified into 4 different categories: no significant uptake if SUVmean was less than SUVmean of the aortic arch (AA); mild if SUVmean was less or equal to 2.5, but higher than SUVmean of the AA; moderate if SUVmean was higher than 2.5, but less or equal to 5; intense if SUVmean was higher than 5.RESULTS: The most intense uptake was observed in the urinary bladder, due to excretion of the radiotracer. No significant uptake was seen in the brain, salivary glands, lungs, myocardium, skeleton, muscles, and fat. Liver, spleen, and adrenal glands had mostly no significant uptake; the gastrointestinal tract had intense physiological uptake, with pancreas being the organ with the highest SUVmax measurements (average SUVmax 64.91). Mild and moderate uptake was measured in the esophagus (average SUVmax 3.99), while the stomach wall, duodenum, and rectum had mild uptake (average SUVmax 2.49, 3.42, and 3.58, respectively).CONCLUSIONS: 68Ga-RM2 has been mostly evaluated for PC detection, but it can be used for other tumors overexpressing GRPR such as breast cancer. This atlas of normal biodistribution and SUV measurements in healthy tissues will help physicians distinguish between physiological vs. pathological uptake, as well as potentially assist with planning future studies using GRPR targeting radiopharmaceuticals.

    View details for DOI 10.1007/s00259-019-04503-4

    View details for PubMedID 31478089

  • F-18-FPPRGD(2) PET/CT in patients with metastatic renal cell cancer EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Toriihara, A., Duan, H., Thompson, H. M., Park, S., Hatami, N., Baratto, L., Fan, A. C., Iagaru, A. 2019; 46 (7): 1518?23
  • Simultaneous PET/MRI in the Evaluation of Breast and Prostate Cancer Using Combined Na[18F] F and [18F]FDG: a Focus on Skeletal Lesions. Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging Sonni, I., Minamimoto, R., Baratto, L., Gambhir, S. S., Loening, A. M., Vasanawala, S. S., Iagaru, A. 2019


    PURPOSE: The purpose of this study is to prospectively evaluate the performance of sodium 18F]fluoride (Na[18F]F)/2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) simultaneous time-of-flight enabled positron emission tomography (PET)/magnetic resonance imaging (MRI) for the detection of skeletal metastases in selected patients with advanced breast and prostate cancers.PROCEDURE: The institutional review board approved this HIPAA-compliant protocol. Written informed consent was obtained from each patient. A total of 74 patients (23 women and 51 men with breast and prostate cancer, respectively) referred for standard-of-care whole-body bone scintigraphy (WBBS) were enrolled in this prospective study. All patients underwent a [99mTc]methyldiphosphonate ([99mTc]MDP) WBBS followed by Na[18F]F/[18F]FDG PET/MRI. Lesions detected by each imaging modality were tabulated and a lesion-based and patient-based analysis was conducted.RESULTS: On a patient-based analysis, [99mTc]MDP WBBS identified skeletal lesions in 37 patients and PET/MRI in 45 patients. On a lesion-based analysis, WBBS identified a total of 81 skeletal lesions, whereas PET/MRI identified 140 lesions. Additionally, PET/MRI showed extra-skeletal lesions in 19 patients, including lymph nodes (16), prostate (4) lung (3), and liver (2) lesions.CONCLUSIONS: The ability of Na[18F]F/[18F]FDG PET/MRI to identify more skeletal lesions than 99mTc-MDP WBBS and to additionally identify extra-skeletal disease may be beneficial for patient care and represent an alternative to the single modalities performed separately. Na[18F]F/[18F]FDG PET/MRI is a promising approach for evaluation of skeletal and extra-skeletal lesions in a selected population of breast and prostate cancer patients.

    View details for DOI 10.1007/s11307-019-01392-9

    View details for PubMedID 31236756

  • 18F-FPPRGD2 PET/CT in patients with metastatic renal cell cancer. European journal of nuclear medicine and molecular imaging Toriihara, A., Duan, H., Thompson, H. M., Park, S., Hatami, N., Baratto, L., Fan, A. C., Iagaru, A. 2019


    PURPOSE: The usefulness of positron emission tomography/computed tomography (PET/CT) using (18F)-2-fluoropropionyl-labeled PEGylated dimeric arginine-glycine-aspartic acid peptide [PEG3-E{c(RGDyk)}2] (18F-FPPRGD2) in patients with metastatic renal cell cancer (mRCC) has not been evaluated; therefore, we were prompted to conduct this pilot study.METHODS: Seven patients with mRCC were enrolled in this prospective study. 18F-FPPRGD2 and 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) PET/CT images were evaluated in a per-lesion analysis. Maximum standardized uptake value (SUVmax) and tumor-to-background ratio (T/B) were measured for all detected lesions, both before and after starting antiangiogenic therapy.RESULTS: Sixty lesions in total were detected in this cohort. SUVmax from 18F-FPPRGD2 PET/CT was lower than that from 18F-FDG PET/CT (4.42.9 vs 7.85.6, P<0.001). Both SUVmax and T/B from 18F-FPPRGD2 PET/CT decreased after starting antiangiogenic therapy (SUVmax, 4.23.2 vs 2.61.4, P=0.003; T/B, 3.73.2 vs 1.50.8, P<0.001). Average changes in SUVmax and T/B were-29.323.6% and-48.128.3%, respectively.CONCLUSIONS: 18F-FPPRGD2 PET/CT may be an useful tool for monitoring early response to antiangiogenic therapy in patients with mRCC. These preliminary results need to be confirmed in larger cohorts.

    View details for PubMedID 30850872

  • Imaging gastrin-releasing peptide receptors (GRPRs) in prostate cancer CLINICAL AND TRANSLATIONAL IMAGING Baratto, L., Laudicella, R., Picchio, M., Baldari, S., Iagaru, A. 2019; 7 (1): 39?44
  • Predicting Response to Immunotherapy by Evaluating Tumors, Lymphoid Cell-Rich Organs, and Immune-Related Adverse Events Using FDG-PET/CT. Clinical nuclear medicine Nobashi, T., Baratto, L., Reddy, S. A., Srinivas, S., Toriihara, A., Hatami, N., Yohannan, T. K., Mittra, E. 2019


    PURPOSE: To investigate whether the evaluation of tumors, lymphoid cell-rich organs, and immune-related adverse events (IRAE) with F-FDG PET/CT can predict the efficacy and outcome of immunotherapy.METHODS: Forty patients who underwent F-FDG-PET/CT scans before and after therapy with immune checkpoint inhibitors from December 2013 to December 2016 were retrospectively enrolled (malignant melanoma, n = 21; malignant lymphoma, n = 11; renal cell carcinoma, n = 8). SUVmax of the baseline and first restaging scans were evaluated in tumors, spleen, bone marrow, thyroid and pituitary glands, and were correlated to best overall response in the first year after therapy; IRAE-affected areas were also evaluated.RESULTS: Interval change between the baseline and first restaging scans showed that patients with a clinical benefit had a significant decrease in tumor parameters (P < 0.001). All patients with an increase of SUVmax in the thyroid of more than 1.5 (n = 5) on the first restaging scan had a complete response (CR) in 1 year. Patients with CR within 1 year (n = 22) were significantly associated with a favorable long-term outcome (P = 0.002). Nine patients with IRAE findings had CR at final evaluation. Among IRAE, thyroiditis was seen significantly earlier than arthritis (P = 0.040).CONCLUSIONS: The decrease of tumor parameters at early time-point PET scans was seen in patients with immunotherapy who had clinical benefit within 1 year. PET-detectable IRAE was useful for prediction of a favorable outcome. Early development of thyroiditis may particularly represent an early response indicator to immunotherapy.

    View details for PubMedID 30688730

  • Prognostic value of somatostatin receptor expressing tumor volume calculated from 68Ga-DOTATATE PET/CT in patients with well-differentiated neuroendocrine tumors. European journal of nuclear medicine and molecular imaging Toriihara, A., Baratto, L., Nobashi, T., Park, S., Hatami, N., Davidzon, G., Kunz, P. L., Iagaru, A. 2019


    To evaluate the prognostic value of volumetric parameters calculated from 68Ga-1,4,7,10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-Thr3-octreotate (68Ga-DOTATATE) positron emission tomography/computed tomography (PET/CT) in patients with well-differentiated neuroendocrine tumor (WD-NET).Ninety-two patients (44 men and 48 women, mean age of 59.5-year-old) with pathologically confirmed WD-NET (grades 1 or 2) were enrolled in a prospective expanded access protocol. Selected data was analyzed retrospectively for this project. Maximum standardized uptake value (SUVmax) in the lesion with the highest 68Ga-DOTATATE uptake was measured and recorded for each patient. In addition, two volumetric parameters, namely, somatostatin receptor expressing tumor volume (SRETV) and total lesion somatostatin receptor expression (TLSRE), were calculated in each 68Ga-DOTATATE-avid lesion. SRETV was defined as tumor volume with higher 68Ga-DOTATATE uptake than the 50% of SUVmax within the volume of interest (VOI) for each lesion. TLSRE was calculated by multiplying SRETV and mean SUV within the same VOI. Thereafter, the sum of SRETV (?SRETV) and TLSRE (?TLSRE) for all detected lesions per patient were calculated. Progression-free survival (PFS) was set as primary endpoint. Kaplan-Meier survival analysis, log-rank test, and Cox's proportional hazard model were used for statistical analysis.Univariate analyses revealed significant difference of PFS for WHO tumor grade and ?SRETV (P??0.05). Multivariate analysis identified WHO tumor grade and ?SRETV as independent predictors of PFS.?SRETV calculated from 68Ga-DOTATATE PET/CT may have prognostic value of PFS in WD-NET patients.

    View details for DOI 10.1007/s00259-019-04455-9

    View details for PubMedID 31350603

  • The Role of PET/CT in the Imaging of Pancreatic Neoplasms. Seminars in ultrasound, CT, and MR Duan, H., Baratto, L., Iagaru, A. 2019; 40 (6): 500?508


    Pancreas cancer is a complex disease and its prognosis is related to the origin of the tumor cell as well as the stage of disease at the time of diagnosis. Pancreatic adenocarcinomas derive from the exocrine pancreas and are the fourth leading cause of cancer-related deaths in the United States, while well-differentiated pancreatic neuroendocrine tumors (pNETs) derived from the endocrine part of the pancreas are rare and characterized by a slow growth and good life expectancy. Surgery is the only curative treatment approach, and an accurate assessment of resectability is of paramount importance in order to avoid futile procedures. The role of molecular imaging with positron emission tomography and computed tomography ranges from indispensable for pNETs to controversial for certain scenarios in pancreatic adenocarcinomas. This review article aims to overview molecular pancreatic imaging.

    View details for DOI 10.1053/j.sult.2019.04.006

    View details for PubMedID 31806148

  • Comparison of three interpretation criteria of 68Ga-PSMA11 PET based on inter- and intra-reader agreement. Journal of nuclear medicine : official publication, Society of Nuclear Medicine Toriihara, A., Nobashi, T., Baratto, L., Duan, H., Moradi, F., Park, S., Hatami, N., Aparici, C., Davidzon, G., Iagaru, A. 2019


    Positron emission tomography (PET) using radiolabeled prostate specific membrane antigen (PSMA) is now more and more widely adopted as a valuable tool to evaluate patients with prostate cancer (PC). Recently, three different criteria for interpretation of PSMA PET were published: European Association of Nuclear Medicine (EANM) criteria, prostate cancer molecular imaging standardized evaluation (PROMISE) criteria, and PSMA-reporting and data system (PSMA-RADS). We compared these three criteria in terms of inter-reader, intra-reader, and inter-criteria agreement. Methods: Data from 104 patients prospectively enrolled in research protocols at our institution were retrospectively reviewed. The cohort consisted of two groups: 47 patients (mean age: 64.2 years old) who underwent Glu-NH-CO-NH-Lys-(Ahx)-[68Ga(HBED-CC)] (68Ga-PSMA11) PET/magnetic resonance imaging (MRI) for initial staging of biopsy-proven intermediate- or high-risk PC, and 57 patients (mean age: 70.5 years old) who underwent 68Ga-PSMA11 PET/computed tomography (CT) due to biochemically recurrent (BCR) PC. Three nuclear medicine physicians independently evaluated all 68Ga-PSMA11 PET/MRI and PET/CT studies according to the three interpretation criteria. Two of them reevaluated all studies 6 months later in the same manner and blinded to the initial reading. Gwet's AC was calculated to evaluate inter- and intra-reader, and inter-criteria agreement based on the following sites: local lesion (primary tumor or prostate bed after radical prostatectomy), lymph node metastases, and other metastases. Results: In the PET/MRI group, inter-reader, intra-reader, and inter-criteria agreements were substantial to almost perfect in any sites according to all of the three criteria. In the PET/CT group, inter-reader agreement was substantial to almost perfect except judgement of distant metastases based on PSMA-RADS (Gwet's AC = 0.57, moderate agreement), in which the most frequent cause of disagreement was lung nodules. Intra-reader agreements were substantial to almost perfect in any sites according to all of the three criteria. Inter-criteria agreements of each site were also substantial to almost perfect. Conclusion: Although the three published criteria have good inter-reader and intra-reader reproducibility in evaluating 68Ga-PSMA11 PET, there are factors bringing inter-reader disagreement. This indicates that further work is needed to address the issue.

    View details for DOI 10.2967/jnumed.119.232504

    View details for PubMedID 31562226

  • Clinical Evaluation of Ga-68-PSMA-Iota Iota and Ga-68-RM2 PET Images Reconstructed With an Improved Scatter Correction Algorithm AMERICAN JOURNAL OF ROENTGENOLOGY Wangerin, K. A., Baratto, L., Khalighi, M., Hope, T. A., Gulaka, P. K., Deller, T. W., Iagaru, A. H. 2018; 211 (3): 655?60


    Gallium-68-labeled radiopharmaceuticals pose a challenge for scatter estimation because their targeted nature can produce high contrast in these regions of the kidneys and bladder. Even small errors in the scatter estimate can result in washout artifacts. Administration of diuretics can reduce these artifacts, but they may result in adverse events. Here, we investigated the ability of algorithmic modifications to mitigate washout artifacts and eliminate the need for diuretics or other interventions.The model-based scatter algorithm was modified to account for PET/MRI scanner geometry and challenges of non-FDG tracers. Fifty-three clinical 68Ga-RM2 and 68Ga-PSMA-11 whole-body images were reconstructed using the baseline scatter algorithm. For comparison, reconstruction was also processed with modified sampling in the single-scatter estimation and with an offset in the scatter tail-scaling process. None of the patients received furosemide to attempt to decrease the accumulation of radiopharmaceuticals in the bladder. The images were scored independently by three blinded reviewers using the 5-point Likert scale.The scatter algorithm improvements significantly decreased or completely eliminated the washout artifacts. When comparing the baseline and most improved algorithm, the image quality increased and image artifacts were reduced for both 68Ga-RM2 and for 68Ga-PSMA-11 in the kidneys and bladder regions.Image reconstruction with the improved scatter correction algorithm mitigated washout artifacts and recovered diagnostic image quality in 68Ga PET, indicating that the use of diuretics may be avoided.

    View details for PubMedID 29873506

  • Prostate Cancer Theranostics Targeting Gastrin-Releasing Peptide Receptors. Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging Baratto, L., Jadvar, H., Iagaru, A. 2018; 20 (4): 501?9


    Gastrin-releasing peptide receptors (GRPRs), part of the bombesin (BBN) family, are aberrantly overexpressed in many cancers, including those of the breast, prostate, pancreas, and lung, and therefore present an attractive target for cancer diagnosis and therapy. Different bombesin analogs have been radiolabeled and used for imaging diagnosis, staging, evaluation of biochemical recurrence, and assessment of metastatic disease in patients with prostate cancer. Recently, interest has shifted from BBN-like receptor agonists to antagonists, because the latter does not induce adverse effects and demonstrate superior in vivo pharmacokinetics. We review the preclinical and clinical literatures on the use of GRPRs as targets for imaging and therapy of prostate cancer, with a focus on the newer developments and theranostic potential of GRPR peptides.

    View details for PubMedID 29256046

  • End-of-treatment and serial PET imaging in primary mediastinal B-cell lymphoma following dose-adjusted EPOCH-R: a paradigm shift in clinical decision making HAEMATOLOGICA Melani, C., Advani, R., Roschewski, M., Walters, K. M., Chen, C. C., Baratto, L., Ahlman, M. A., Miljkovic, M. D., Steinberg, S. M., Lam, J., Shovlin, M., Dunleavy, K., Pittaluga, S., Jaffe, E. S., Wilson, W. H. 2018; 103 (8): 1337?44


    Dose-adjusted-EPOCH-R obviates the need for radiotherapy in most patients with primary mediastinal B-cell lymphoma. End-of-treatment PET, however, does not accurately identify patients at risk of treatment failure, thereby confounding clinical decision making. To define the role of PET in primary mediastinal B-cell lymphoma following dose-adjusted-EPOCH-R, we extended enrollment and follow up on our published phase II trial and independent series. Ninety-three patients received dose-adjusted-EPOCH-R without radiotherapy. End-of-treatment PET was performed in 80 patients, of whom 57 received 144 serial scans. One nuclear medicine physician from each institution blindly reviewed all scans from their respective institution. End-of-treatment PET was negative (Deauville 1-3) in 55 (69%) patients with one treatment failure (8-year event-free and overall survival of 96.0% and 97.7%). Among 25 (31%) patients with a positive (Deauville 4-5) end-of-treatment PET, there were 5 (20%) treatment failures (8-year event-free and overall survival of 71.1% and 84.3%). Linear regression analysis of serial scans showed a significant decrease in SUVmax in positive end-of-treatment PET non-progressors compared to an increase in treatment failures. Among 6 treatment failures, the median end-of-treatment SUVmax was 15.4 (range, 1.9-21.3), and 4 achieved long-term remission with salvage therapy. Virtually all patients with a negative end-of-treatment PET following dose-adjusted-EPOCH-R achieved durable remissions and should not receive radiotherapy. Among patients with a positive end-of-treatment PET, only 5/25 (20%) had treatment-failure. Serial PET imaging distinguished end-of-treatment PET positive patients without treatment failure, thereby reducing unnecessary radiotherapy by 80%, and should be considered in all patients with an initial positive PET following dose-adjusted-EPOCH-R ( identifier 00001337).

    View details for PubMedID 29748435

  • 18F-florbetaben whole-body PET/MRI for evaluation of systemic amyloid deposition. EJNMMI research Baratto, L., Park, S. Y., Hatami, N., Gulaka, P., Vasanawala, S., Yohannan, T. K., Herfkens, R., Witteles, R., Iagaru, A. 2018; 8 (1): 66


    BACKGROUND: Florbetaben, a 18F-labeled stilbene derivative (Neuraceq, formerly known as BAY-949172), is a diagnostic radiopharmaceutical developed to visualize beta-amyloid plaques in the brain. Here, we report a pilot study evaluating patients with suspected cardiac amyloidosis for systemic extent of disease.METHODS: We prospectively enrolled nine patients, 61-86year old (meanSD 69.48.6), referred from the cardiac amyloid clinic. First, dynamic imaging of the heart was acquired immediately after injection of 222-318.2MBq (meanSD 270.133.3) of 18F-florbetaben using the GE SIGNA PET/MRI. This was followed by a whole-body PET/MRI scan 60-146.4min (meanSD 9833.4) after injection. Cardiac MRI sequences included ECG-triggered cine SSFP, T2-weighted, and late gadolinium-enhanced imaging. Whole-body MRI sequences included MRAC and axial T1-weighted imaging.RESULTS: High early uptake and delayed high uptake in the left ventricle correlated with amyloid deposition in five patients, while low uptake on early and delayed cardiac imaging was noted in four patients. Cardiac function measurements were successfully obtained in all participants. Areas of increased abnormal 18F-florbetaben accumulation were noted on delayed whole-body imaging in the bone marrow (seven patients), stomach (diffuse in five patients and focal in one patient), brain (five patients), salivary glands (three patients), tongue (three patients), spleen (three patients), skeletal muscles (three patients), ocular muscles (two patients), thyroid (two patients), pleura (two patients), kidneys (two patients), and lungs (two patients).CONCLUSIONS: Whole-body 18F-florbetaben PET/MRI is promising for localization of systemic amyloid deposition. This technique may provide important structural and functional information regarding the organs involved by disease, with potential to guide biopsy and evaluate response to treatment.TRIAL REGISTRATION: registration: NCT03119558 .

    View details for PubMedID 30043115

  • Initial experience with a SiPM-based PET/CT scanner: influence of acquisition time on image quality EJNMMI PHYSICS Sonni, I., Baratto, L., Park, S., Hatami, N., Srinivas, S., Davidzon, G., Gambhir, S., Iagaru, A. 2018; 5: 9


    A newly introduced PET/CT scanner (Discovery Meaningful Insights-DMI, GE Healthcare) includes the silicon photomultiplier (SiPM) with time-of-flight (TOF) technology first used in the GE SIGNA PET/MRI. In this study, we investigated the impact of various acquisition times on image quality using this SiPM-based PET/CT.We reviewed data from 58 participants with cancer who were scanned using the DMI PET/CT scanner. The administered dosages ranged 295.3-429.9MBq (mean??SD 356.3??37.4) and imaging started at 71-142min (mean??SD 101.41??17.52) after administration of the radiopharmaceutical. The patients' BMI ranged 19.79-46.16 (mean??SD 26.55??5.53). We retrospectively reconstructed the raw TOF data at 30, 60, 90, and 120s/bed and at the standard image acquisition time per clinical protocol (180 or 210s/bed depending on BMI). Each reconstruction was reviewed blindly by two nuclear medicine physicians and scored 1-5 (1-poor, 5-excellent quality). The liver signal-to-noise ratio (SNR) was used as a quantitative measure of image quality.The average scores??SD of the readers were 2.61??0.83, 3.70?0.92, 4.36??0.82, 4.82??0.39, and 4.91??0.91 for the 30, 60, 90, and 120s/bed and at standard acquisition time, respectively. Inter-reader agreement on image quality assessment was good, with a weighted kappa of 0.80 (95% CI 0.72-0.81). In the evaluation of the effects of time per bed acquisition on semi-quantitative measurements, we found that the only time point significantly different from the standard time were 30 and 60s (both with P??25, images can be acquired as fast as 90s/bed using the SiPM PET/CT and still result in very good image quality (average score >?4).

    View details for PubMedID 29666972

  • Sentinel node biopsy in endometrial cancer: an update CLINICAL AND TRANSLATIONAL IMAGING Crivellaro, C., Baratto, L., Dolci, C., De Ponti, E., Magni, S., Elisei, F., Papadia, A., Buda, A. 2018; 6 (2): 91?100
  • Comparison Between Different PET and CT-Based Imaging Interpretation Criteria at Interim Imaging in Patients With Diffuse Large B-Cell Lymphoma CLINICAL NUCLEAR MEDICINE Baratto, L., Davidzon, G. A., Moghbel, M., Hatami, N., Iagaru, A., Mittra, E. S. 2018; 43 (1): 1?8


    To evaluate the predictive value of interim PET (iPET) in diffuse large B-cell lymphoma (DLBCL) using 5 different imaging interpretation criteria: Deauville 5-point scale criteria, International Harmonization Project (IHP) criteria, Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, European Organization for Research and Treatment of Cancer, and PET Response Criteria in Solid Tumors (PERCIST) 1.0.We retrospectively reviewed records from 38 patients with DLBCL who underwent baseline and iPET at our institution. Imaging was interpreted according to the previously mentioned criteria. Results were correlated with end-of-treatment response, based on reports at the end of treatment radiological examinations, overall survival (OS), and progression-free survival (PFS) to assess and compare the predictive value of iPET according to each criterion. We also evaluated the concordance between different criteria.The Deauville and PERCIST criteria were the most reliable for predicting end-of-treatment response, reporting an accuracy of 81.6%. They also correlated with OS and PFS (P = 0.0004 and P = 0.0001, and P = 0.0007 and P = 0.0002, for Deauville and PERCIST, respectively). Interim PET according to European Organization for Research and Treatment of Cancer also predicted the end-of-treatment response with an accuracy of 73.7% and had a significant correlation with OS (P = 0.007) and PFS (P = 0.007). In contrast, the IHP criteria and RECIST did not predict outcomes: the accuracy for end-of-treatment response was 34.2% and 36.8%, respectively, with no significant correlation with OS or PFS (P = 0.182 and P = 0.357, and P = 0.341 and P = 0.215, for OS and PFS, respectively).The predictive value of iPET in DLBCL patients is most reliable using the Deauville and PERCIST criteria. Criteria that rely on anatomical characteristics, namely, RECIST and IHP criteria, are less accurate in predicting patient outcomes in DLBCL.

    View details for DOI 10.1097/RLU.0000000000001880

    View details for Web of Science ID 000418319900001

    View details for PubMedID 29076913

  • Role of Imaging in Early-Phase Trials NOVEL DESIGNS OF EARLY PHASE TRIALS FOR CANCER THERAPEUTICS Greene, L., Srinivas, S., Park, S., Hatami, N., Nobashi, T., Baratto, L., Toriihara, A., Gambhir, S. S., Kummar, S., Takimoto, C. 2018: 129?49
  • Imaging of Prostate Cancer Using Gallium-68-Labeled Bombesin. PET clinics Sonni, I., Baratto, L., Iagaru, A. 2017; 12 (2): 159-171


    Nuclear medicine can play an important role in evaluating prostate cancer combining anatomical and functional information with hybrid techniques. Various PET radiopharmaceuticals have been used for targeting specific biological markers in prostate cancer. Research is ideally oriented towards the development of radiopharmaceuticals targeting antigens overexpressed in prostate cancer, as opposed to normal prostate tissue. In this regard, gastrin-releasing peptide receptors (GRPR) are excellent candidates. Bombesin analogues targeting the GRPR have been investigated. Gallium-68 ((68)Ga) is an interesting PET radioisotope due to several advantages, such as availability, ease of radiochemistry, half-life, and costs. The focus of this review is on (68)Ga-labeled bombesin analogues in prostate cancer.

    View details for DOI 10.1016/j.cpet.2016.11.003

    View details for PubMedID 28267450

  • 18F-FDG silicon photomultiplier PET/CT: A pilot study comparing semi-quantitative measurements with standard PET/CT. PloS one Baratto, L., Park, S. Y., Hatami, N., Davidzon, G., Srinivas, S., Gambhir, S. S., Iagaru, A. 2017; 12 (6)


    To evaluate if the new Discovery Molecular Insights (DMI) PET/CT scanner provides equivalent results compared to the standard of care PET/CT scanners (GE Discovery 600 or GE Discovery 690) used in our clinic and to explore any possible differences in semi-quantitative measurements.The local Institutional Review Board approved the protocol and written informed consent was obtained from each patient. Between September and November 2016, 50 patients underwent a single 18F-FDG injection and two scans: the clinical standard PET/CT followed immediately by the DMI PET/CT scan. We measured SUVmax and SUVmean of different background organs and up to four lesions per patient from data acquired using both scanners.DMI PET/CT identified all the 107 lesions detected by standard PET/CT scanners, as well as additional 37 areas of focal increased 18F-FDG uptake. The SUVmax values for all 107 lesions ranged 1.2 to 14.6 (mean SD: 2.8 2.8), higher on DMI PET/CT compared with standard of care PET/CT. The mean lesion:aortic arch SUVmax ratio and mean lesion:liver SUVmax ratio were 0.2-15.2 (mean SD: 3.2 2.6) and 0.2-8.5 (mean SD: 1.9 1.4) respectively, higher on DMI PET/CT than standard PET/CT. These differences were statistically significant (P value < 0.0001) and not correlated to the delay in acquisition of DMI PET data (P < 0.0001).Our study shows high performance of the new DMI PET/CT scanner. This may have a significant role in diagnosing and staging disease, as well as for assessing and monitoring responses to therapies.

    View details for DOI 10.1371/journal.pone.0178936

    View details for PubMedID 28582472

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