Research Focus: Molecular Imaging, PET, Oncology, Immunology, T cell imaging

Research Scientist, Department of Radiology, Stanford (2016-present)
Post-Doctoral Scholar, Department of Radiology, Stanford (2015-2016)
Visiting Researcher, Plateforme d'imagerie dynamique, Pasteur Institute (2014)
Post-Doctoral Research Associate, Comprehensive Cancer Imaging Centre, Imperial College London (2010)

Honors & Awards

  • Science and Technology Travel Fellow, Winston Churchill Memorial Trust (2014)
  • Travel Award, World Molecular Imaging Congress-Kyoto, Japan (2010)
  • Travel Award, World Molecular Imaging Congress-Montreal, Canada (2009)
  • Travel Award, World Molecular Imaging Congress-Nice, France (2008)
  • Governor's Prize Class Valedictorian and First Class Honors, Imperial College London (2005)


  • Israt Alam. "United States Patent US-2018-0043040-A1 Imaging tumor glycolysis by non-invasive measurement of pyruvate kinase M2.", Feb 15, 2018
  • Israt Alam, Maaike de Backer, Andre Neves, Kevin Brindle. "United Kingdom Patent Europe EP2280735 Agents for detecting and imaging cell death", University of Cambridge, Apr 29, 2009


Professional Affiliations and Activities

  • Course Co-Director, BioE 224 (2017 - Present)
  • Course Faculty, BioE 224 (2016 - Present)


All Publications

  • Intraoperative Molecular Imaging in Lung Cancer: The State of the Art and the Future MOLECULAR THERAPEUTICS Rogalla, S., Joosten, S. S., Alam, I. S., Gambhir, S. S., Vermesh, O. 2018; 7 (26): 338-341
  • Eradication of spontaneous malignancy by local immunotherapy. SCIENCE TRANSLATIONAL MEDICINE Sagiv-Barfi, I., Czerwinski, D., Levy, S., Alam, I. S., Mayer, A. T., Gambhir, S. S., Levy, R. 2018; 10 (426)
  • [18F]FSPG-PET imaging reflects up-regulation of the cystine-glutamate exchanger in CNS tissues in a mouse model of multiple sclerosis. JOURNAL OF NEUROINFLAMMATION Hoehne, A., James, M. L., Alam, I. S., Ronald, J., Schneider, B., D'Souza, A., Witney , T. H., Andrews , L. E., Cropper, H., Behera, D., Gowrishankar, G., Ding, Z., Wyss-Coray, T., Chin, . T., Biswal, S., Gambhir, S. S. 2018
  • A PET Imaging Strategy to Visualize Activated T Cells in Acute Graft-versus-Host Disease Elicited by Allogenic Hematopoietic Cell Transplant. Cancer research Ronald, J. A., Kim, B., Gowrishankar, G., Namavari, M., Alam, I. S., D'Souza, A., Nishikii, H., Chuang, H., Ilovich, O., Lin, C., Reeves, R., Shuhendler, A., Hoehne, A., Chan, C. T., Baker, J., Yaghoubi, S. S., VanBrocklin, H. F., Hawkins, R., Franc, B. L., Jivan, S., Slater, J. B., Verdin, E. F., Gao, K. T., Benjamin, J., Negrin, R., Gambhir, S. S. 2017; 77 (11): 2893-2902


    A major barrier to successful use of allogeneic hematopoietic cell transplantation is acute graft-versus-host disease (aGVHD), a devastating condition that arises when donor T cells attack host tissues. With current technologies, aGVHD diagnosis is typically made after end-organ injury and often requires invasive tests and tissue biopsies. This affects patient prognosis as treatments are dramatically less effective at late disease stages. Here, we show that a novel PET radiotracer, 2'-deoxy-2'-[18F]fluoro-9-β-D-arabinofuranosylguanine ([18F]F-AraG), targeted toward two salvage kinase pathways preferentially accumulates in activated primary T cells. [18F]F-AraG PET imaging of a murine aGVHD model enabled visualization of secondary lymphoid organs harboring activated donor T cells prior to clinical symptoms. Tracer biodistribution in healthy humans showed favorable kinetics. This new PET strategy has great potential for early aGVHD diagnosis, enabling timely treatments and improved patient outcomes. [18F]F-AraG may be useful for imaging activated T cells in various biomedical applications. Cancer Res; 77(11); 2893-902. ©2017 AACR.

    View details for DOI 10.1158/0008-5472.CAN-16-2953

    View details for PubMedID 28572504

  • F]DASA-23 for Imaging Tumor Glycolysis Through Noninvasive Measurement of Pyruvate Kinase M2. Molecular imaging and biology Beinat, C., Alam, I. S., James, M. L., Srinivasan, A., Gambhir, S. S. 2017


    A hallmark of cancer is metabolic reprogramming, which is exploited by cancer cells to ensure rapid growth and survival. Pyruvate kinase M2 (PKM2) catalyzes the final step in glycolysis, a key step in tumor metabolism and growth. Recently, we reported the radiosynthesis of the first positron emission tomography tracer for visualizing PKM2 in vivo-i.e., [(11)C]DASA-23. Due to the highly promising imaging results obtained with [(11)C]DASA-23 in rodent model glioblastoma, we set out to generate an F-18-labeled version of this tracer, with the end goal of clinical translation in mind. Herein, we report the radiosynthesis of 1-((2-fluoro-6-[(18)F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([(18)F]DASA-23) and our initial investigation of its binding properties in cancer cells.We synthesized [(18)F]DASA-23 via fluorination of 1-((2-fluoro-6-nitrophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine (10) with K[(18)F]F/K2.2.2 in N,N-dimethylformamide at 110 °C for 20 min. Subsequently, we evaluated uptake of [(18)F]DASA-23 in HeLa cervical adenocarcinoma cells and in vitro stability in human and mouse serum.We successfully prepared [(18)F]DASA-23 in 2.61 ± 1.54 % radiochemical yield (n = 10, non-decay corrected at end of synthesis) with a specific activity of 2.59 ± 0.44 Ci/μmol. Preliminary cell uptake experiments revealed high uptake in HeLa cells, which was effectively blocked by pretreating cells with the structurally distinct PKM2 activator, TEPP-46. [(18)F]DASA-23 remained intact in human and mouse serum up to 120 min.Herein, we have identified a F-18-labeled PKM2 specific radiotracer which shows potential for in vivo imaging. The promising cell uptake results reported herein warrant the further evaluation of [(18)F]DASA-23 for its ability to detect and monitor cancer noninvasively.

    View details for DOI 10.1007/s11307-017-1068-8

    View details for PubMedID 28236227

  • Rapid Imaging of Tumor Cell Death in vivo using the C2A domain of Synaptotagmin-I JOURNAL OF NUCLEAR MEDICINE Neves, A. A., Xie, ., Fawcett, S., Alam, I. S., Witney, T. H., Lewis, D. Y., Brindle, K. M. 2017
  • Microwave gallium-68 radiochemistry for kinetically stable bis(thiosemicarbazone) complexes: structural investigations and cellular uptake under hypoxia DALTON TRANSACTIONS Alam, I. S., Arrowsmith, R. L., Cortezon-Tamarit, F., Twyman, F., Kociok-Koehn, G., Botchway, S. W., Dilworth, J. R., Carroll, L., Aboagye, E. O., Pascu, S. I. 2016; 45 (1): 144-155

    View details for DOI 10.1039/c5dt02537k

    View details for Web of Science ID 000366429000017

  • Radiopharmaceuticals as probes to characterize tumour tissue EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING Alam, I. S., Arshad, M. A., Quang-De Nguyen, Q. D., Aboagye, E. O. 2015; 42 (4): 537-561
  • Acetyl-CoA Synthetase 2 Promotes Acetate Utilization and Maintains Cancer Cell Growth under Metabolic Stress CANCER CELL Schug, Z. T., Peck, B., Jones, D. T., Zhang, Q., Grosskurth, S., Alam, I. S., Goodwin, L. M., Smethurst, E., Mason, S., Blyth, K., McGarry, L., James, D., Shanks, E., Kalna, G., Saunders, R. E., Jiang, M., Howell, M., Lassailly, F., Thin, M. Z., Spencer-Dene, B., Stamp, G., van den Broek, N. J., Mackay, G., Bulusu, V., Kamphorst, J. J., Tardito, S., Strachan, D., Harris, A. L., Aboagye, E. O., Critchlow, S. E., Wakelam, M. J., Schulze, A., Gottlieb, E. 2015; 27 (1): 57-71


    A functional genomics study revealed that the activity of acetyl-CoA synthetase 2 (ACSS2) contributes to cancer cell growth under low-oxygen and lipid-depleted conditions. Comparative metabolomics and lipidomics demonstrated that acetate is used as a nutritional source by cancer cells in an ACSS2-dependent manner, and supplied a significant fraction of the carbon within the fatty acid and phospholipid pools. ACSS2 expression is upregulated under metabolically stressed conditions and ACSS2 silencing reduced the growth of tumor xenografts. ACSS2 exhibits copy-number gain in human breast tumors, and ACSS2 expression correlates with disease progression. These results signify a critical role for acetate consumption in the production of lipid biomass within the harsh tumor microenvironment.

    View details for DOI 10.1016/j.ccell.2014.12.002

    View details for Web of Science ID 000347906900010

    View details for PubMedID 25584894

  • Preclinical Evaluation of 3-F-18-Fluoro-2,2-Dimethylpropionic Acid as an Imaging Agent for Tumor Detection JOURNAL OF NUCLEAR MEDICINE Witney, T. H., Pisaneschi, F., Alam, I. S., Trousil, S., Kaliszczak, M., Twyman, F., Brickute, D., Nguyen, Q., Schug, Z., Gottlieb, E., Aboagye, E. O. 2014; 55 (9): 1506-1512


    Deregulated cellular metabolism is a hallmark of many cancers. In addition to increased glycolytic flux, exploited for cancer imaging with (18)F-FDG, tumor cells display aberrant lipid metabolism. Pivalic acid is a short-chain, branched carboxylic acid used to increase oral bioavailability of prodrugs. After prodrug hydrolysis, pivalic acid undergoes intracellular metabolism via the fatty acid oxidation pathway. We have designed a new probe, 3-(18)F-fluoro-2,2-dimethylpropionic acid ((18)F-FPIA), for the imaging of aberrant lipid metabolism and cancer detection.Cell intrinsic uptake of (18)F-FPIA was measured in murine EMT6 breast adenocarcinoma cells. In vivo dynamic imaging, time course biodistribution, and radiotracer stability testing were performed. (18)F-FPIA tumor retention was further compared in vivo to (18)F-FDG uptake in several xenograft models and inflammatory tissue.(18)F-FPIA rapidly accumulated in EMT6 breast cancer cells, with retention of intracellular radioactivity predicted to occur via a putative (18)F-FPIA carnitine-ester. The radiotracer was metabolically stable to degradation in mice. In vivo imaging of implanted EMT6 murine and BT474 human breast adenocarcinoma cells by (18)F-FPIA PET showed rapid and extensive tumor localization, reaching 9.1% ± 0.5% and 7.6% ± 1.2% injected dose/g, respectively, at 60 min after injection. Substantial uptake in the cortex of the kidney was seen, with clearance primarily via urinary excretion. Regarding diagnostic utility, uptake of (18)F-FPIA was comparable to that of (18)F-FDG in EMT6 tumors but superior in the DU145 human prostate cancer model (54% higher uptake; P = 0.002). Furthermore, compared with (18)F-FDG, (18)F-FPIA had lower normal-brain uptake resulting in a superior tumor-to-brain ratio (2.5 vs. 1.3 in subcutaneously implanted U87 human glioma tumors; P = 0.001), predicting higher contrast for brain cancer imaging. Both radiotracers showed increased localization in inflammatory tissue.(18)F-FPIA shows promise as an imaging agent for cancer detection and warrants further investigation.

    View details for DOI 10.2967/jnumed.114.140343

    View details for Web of Science ID 000341286900019

    View details for PubMedID 25012458

  • Radiolabeled RGD Tracer Kinetics Annotates Differential alpha(v)beta(3) Integrin Expression Linked to Cell Intrinsic and Vessel Expression MOLECULAR IMAGING AND BIOLOGY Alam, I. S., Witney, T. H., Tomasi, G., Carroll, L., Twyman, F. J., Quang-De Nguyen, Q. D., Aboagye, E. O. 2014; 16 (4): 558-566
  • A Novel Radiotracer to Image Glycogen Metabolism in Tumors by Positron Emission Tomography CANCER RESEARCH Witney, T. H., Carroll, L., Alam, I. S., Chandrashekran, A., Quang-De Nguyen, Q. D., Sala, R., Harris, R., DeBerardinis, R. J., Agarwal, R., Aboagye, E. O. 2014; 74 (5): 1319-1328


    The high rate of glucose uptake to fuel the bioenergetic and anabolic demands of proliferating cancer cells is well recognized and is exploited with (18)F-2-fluoro-2-deoxy-d-glucose positron emission tomography ((18)F-FDG-PET) to image tumors clinically. In contrast, enhanced glucose storage as glycogen (glycogenesis) in cancer is less well understood and the availability of a noninvasive method to image glycogen in vivo could provide important biologic insights. Here, we demonstrate that (18)F-N-(methyl-(2-fluoroethyl)-1H-[1,2,3]triazole-4-yl)glucosamine ((18)F-NFTG) annotates glycogenesis in cancer cells and tumors in vivo, measured by PET. Specificity of glycogen labeling was demonstrated by isolating (18)F-NFTG-associated glycogen and with stable knockdown of glycogen synthase 1, which inhibited (18)F-NFTG uptake, whereas oncogene (Rab25) activation-associated glycogen synthesis led to increased uptake. We further show that the rate of glycogenesis is cell-cycle regulated, enhanced during the nonproliferative state of cancer cells. We demonstrate that glycogen levels, (18)F-NFTG, but not (18)F-FDG uptake, increase proportionally with cell density and G1-G0 arrest, with potential application in the assessment of activation of oncogenic pathways related to glycogenesis and the detection of posttreatment tumor quiescence. Cancer Res; 74(5); 1319-28. ©2014 AACR.

    View details for DOI 10.1158/0008-5472.CAN-13-2768

    View details for Web of Science ID 000332475900006

    View details for PubMedID 24590807

  • RGD-targeted MnO nanoparticles as T-1 contrast agents for cancer imaging - the effect of PEG length in vivo JOURNAL OF MATERIALS CHEMISTRY B Gallo, J., Alam, I. S., Lavdas, I., Wylezinska-Arridge, M., Aboagye, E. O., Long, N. J. 2014; 2 (7): 868-876

    View details for DOI 10.1039/c3tb21422b

    View details for Web of Science ID 000330118500012

  • PET imaging with multimodal upconversion nanoparticles DALTON TRANSACTIONS Gallo, J., Alam, I. S., Jin, J., Gu, Y., Aboagye, E. O., Wong, W., Long, N. J. 2014; 43 (14): 5535-5545


    A series of new upconversion nanoparticles have been functionalised with tumour-targeting molecules and metal chelates, prepared following standard peptidic and thiol chemistry. The targeting strategy has been delivered via the αvβ3 integrin, which is a heterodimeric cell surface receptor that is up-regulated in a variety of cancers, such as melanoma and breast cancer. The well-known DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) motif allows coordination to the radionuclide (68)Ga. Radiolabelling experiments were optimised under relatively mild conditions, and are rare amongst nanoparticulate materials. In vivo application of these probes in mouse tumour models revealed their potential as specific cancer contrast agents for PET imaging.

    View details for DOI 10.1039/c3dt53095g

    View details for Web of Science ID 000332929200033

    View details for PubMedID 24535647

  • Evaluation of Deuterated F-18- and C-11-Labeled Choline Analogs for Cancer Detection by Positron Emission Tomography CLINICAL CANCER RESEARCH Witney, T. H., Alam, I. S., Turton, D. R., Smith, G., Carroll, L., Brickute, D., Twyman, F. J., Quang-De Nguyen, Q. D., Tomasi, G., Awais, R. O., Aboagye, E. O. 2012; 18 (4): 1063-1072


    (11)C-Choline-positron emission tomography (PET) has been exploited to detect the aberrant choline metabolism in tumors. Radiolabeled choline uptake within the imaging time is primarily a function of transport, phosphorylation, and oxidation. Rapid choline oxidation, however, complicates interpretation of PET data. In this study, we investigated the biologic basis of the oxidation of deuterated choline analogs and assessed their specificity in human tumor xenografts.(11)C-Choline, (11)C-methyl-[1,2-(2)H(4)]-choline ((11)C-D4-choline), and (18)F-D4-choline were synthesized to permit comparison. Biodistribution, metabolism, small-animal PET studies, and kinetic analysis of tracer uptake were carried out in human colon HCT116 xenograft-bearing mice.Oxidation of choline analogs to betaine was highest with (11)C-choline, with reduced oxidation observed with (11)C-D4-choline and substantially reduced with (18)F-D4-choline, suggesting that both fluorination and deuteration were important for tracer metabolism. Although all tracers were converted intracellularly to labeled phosphocholine (specific signal), the higher rate constants for intracellular retention (K(i) and k(3)) of (11)C-choline and (11)C-D4-choline, compared with (18)F-D4-choline, were explained by the rapid conversion of the nonfluorinated tracers to betaine within HCT116 tumors. Imaging studies showed that the uptake of (18)F-D4-choline in three tumors with similar radiotracer delivery (K(1)) and choline kinase α expression-HCT116, A375, and PC3-M-were the same, suggesting that (18)F-D4-choline has utility for cancer detection irrespective of histologic type.We have shown here that both deuteration and fluorination combine to provide protection against choline oxidation in vivo. (18)F-D4-choline showed the highest selectivity for phosphorylation and warrants clinical evaluation.

    View details for DOI 10.1158/1078-0432.CCR-11-2462

    View details for Web of Science ID 000300628100016

    View details for PubMedID 22235095

  • Imaging sialylated tumor cell glycans in vivo FASEB JOURNAL Neves, A. A., Stoeckmann, H., Harmston, R. R., Pryor, H. J., Alam, I. S., Ireland-Zecchini, H., Lewis, D. Y., Lyons, S. K., Leeper, F. J., Brindle, K. M. 2011; 25 (8): 2528-2537


    Cell surface glycans are involved in numerous physiological processes that involve cell-cell interactions and migration, including lymphocyte trafficking and cancer metastasis. We have used a bioorthogonal metabolic labeling strategy to detect cell surface glycans and demonstrate, for the first time, fluorescence and radionuclide imaging of sialylated glycans in a murine tumor model in vivo. Peracetylated azido-labeled N-acetyl-mannosamine, injected intraperitoneally, was used as the metabolic precursor for the biosynthesis of 5-azidoneuraminic, or azidosialic acid. Azidosialic acid-labeled cell surface glycans were then reacted, by Staudinger ligation, with a biotinylated phosphine injected intraperitoneally, and the biotin was detected by subsequent intravenous injection of a fluorescent or radiolabeled avidin derivative. At 24 h after administration of NeutrAvidin, labeled with either a far-red fluorophore or (111)In, there was a significant azido-labeled N-acetyl-mannosamine-dependent increase in tumor-to-tissue contrast, which was detected using optical imaging or single-photon-emission computed tomography (SPECT), respectively. The technique has the potential to translate to the clinic, where, given the prognostic relevance of altered sialic acid expression in cancer, it could be used to monitor disease progression.

    View details for DOI 10.1096/fj.10-178590

    View details for Web of Science ID 000293337800004

    View details for PubMedID 21493886

  • Comparison of the C2A Domain of Synaptotagmin-I and Annexin-V As Probes for Detecting Cell Death BIOCONJUGATE CHEMISTRY Alam, I. S., Neves, A. A., Witney, T. H., Boren, J., Brindle, K. M. 2010; 21 (5): 884-891


    The induction of apoptosis is frequently accompanied by the exposure of phosphatidylserine (PS) on the cell surface, which has been detected using radionuclide and fluorescently labeled derivatives of the PS-binding protein, Annexin V. The fluorescently labeled protein has been used extensively in vitro as a diagnostic reagent for detecting cell death, and radionuclide-labeled derivatives have undergone clinical trials for detecting tumor cell death in vivo following treatment. We show here that the C2A domain of Synaptotagmin-I, which had been fluorescently labeled at a single cysteine residue introduced by site-directed mutagenesis, detected the same levels of cell death as a similarly labeled Annexin-V derivative, in drug-treated murine lymphoma and human breast cancer cell lines in vitro. However, the C2A derivative showed significantly less binding to viable cells and, as a consequence, up to 4-fold more specific binding to apoptotic and necrotic cells when compared with Annexin-V. C2A offers a potential route for the development of a new generation of more specific imaging probes for the detection of tumor cell death in the clinic.

    View details for DOI 10.1021/bc9004415

    View details for Web of Science ID 000277683300013

    View details for PubMedID 20402461