Robert Flavell, MD, PhD

Assistant Professor
Assistant Director, Nuclear Medicine Residency & Fellowship Programs
Asst Professor in Residence

Biography

Robert Flavell, MD, PhD, is an Assistant Professor in the Nuclear Medicine subspecialty in the Department of Radiology and Biomedical Imaging at the University of California, San Francisco. He received his medical degree from Weill Cornell Medical College, and his PhD from the Rockefeller University as part of the Tri-Institutional MD PhD program. He completed his one-year internship at the Memorial Sloan­Kettering Cancer Center in New York. Dr. Flavell completed a four-year diagnostic radiology residency at the University of California, San Francisco, where he also finished a Nuclear Medicine fellowship. In June 2016. he joined the faculty as an Assistant Professor in Residence.

Dr. Flavell’s laboratory focuses on the development of new molecular imaging tools for better understanding of disease progression in patients with prostate and other cancers. One area of interest is the relationship between acidic interstitial pH and disease progression. Solid tumors are poorly perfused and secrete acids into the adjacent interstitium, resulting in a pH which is mildly acidic, typically ranging from 6.5 – 7.0. This property has been associated with high-grade malignancy, local invasion, and metastasis in animal models. Therefore, it would be desirable to have a method which could be used in patients for monitoring tissue pH. Therefore, one focus of Dr. Flavell’s research is developing methods of imaging acidic interstitial pH with potential for clinical translation. Specifically, two methods are being developed, one of which permits whole body evaluation of areas of acidic pH using positron emission tomography (PET) imaging, and one method which permits quantitative, local determination of interstitial pH based on hyperpolarized 13C magnetic resonance spectroscopy (HP-MRS). The PET method is based on pro-drug glycosylamine derivatives of the commonly used oncologic tracer, [18F]FDG, termed [18F]FDG amines, which are blocked with an acid-labile protecting group. When exposed to the mildly acidic pH present in the interstitium of a solid tumor, the caging group decomposes, liberating native [18F]FDG, which is subsequently absorbed by the adjacent cancer cell (Flavell R.R. et al., Bioconjugate Chem., 2016). The HP-MRS method is based on the administration of a 13C labeled probe which has a predictable change in its chemical shift based on pH. By comparison to a standard curve, quantitative pH measurements can be obtained (Flavell R.R. et al. Chem. Comm. 2015). These techniques are being optimized and ongoing directions include application in animal models, with the long term goal of clinical translation. Other areas of developing interest in the laboratory include techniques for imaging of metals in the microenvironment, and imaging of a metabolic signature associated with immune activation.

Expertise:
Nuclear Medicine

Specialty:
Novel radiotracer development, oncologic imaging, PET imaging, hyperpolarized 13C magnetic resonance imaging

Professional Interests:
Radiology, molecular imaging, PET imaging, prostate cancer, nuclear medicine, radiochemistry, hyperpolarized 13C magnetic resonance imaging

Education and Training:
• Medical School: Weill Cornell Medical College, New York
• PhD: The Rockefeller University, New York
• Internship: Memorial Sloan­-Kettering Cancer Center, New York
• Residency: University of California, San Francisco
• Fellowship: University of California, San Francisco – Nuclear Medicine

Honors and Awards

David Blitzer Young Investigator Award, Prostate Cancer Foundation, 2017-2020
Howard S. Stern Research Award, Society of Abdominal Radiology, 2017-2019
New Directions in Prostate Cancer Research Award, University of California, San Francisco, 2017
Research Program Physician Research Training Grant, Department of Defense Prostate Cancer, 2016
Runner up, Surbeck Scholar Award, University of California, San Francisco, 2016
Research Scholar Program, Association of University Radiologists / American College of Radiology, 2015
Certificate of Merit, Radiology Society of North America (RSNA), 2015
T32 Training Grant, National Institute of Biomedical Imaging and Bioengineering (NIBIB), 2014
Certificate of Merit, Radiology Society of North America (RSNA), 2014
Catalyst Consultation Award, University of California, San Francisco Catalyst Program, 2014
Introduction to Academic Radiology Program, American Roentgen Ray Society, 2013

Publications

Korenchan DE, Gordon JW, Subramaniam S, Sriram R, Baligand C, VanCriekinge M, Bok R, Vigneron DB, Wilson DM, Larson PEZ, Kurhanewicz J, Flavell RR. Using bidirectional chemical exchange for improved hyperpolarized [13 C]bicarbonate pH imaging. Magn Reson Med. 2019 May 03.
Raghavan K, Wen KW, Small EJ, Ha P, Flavell RR. Incidentally Detected Oropharyngeal Squamous Cell Carcinoma on 18F-Fluciclovine PET/CT. Clin Nucl Med. 2019 May; 44(5):e367-e369.
Lawhn-Heath C, Flavell RR, Behr SC, Yohannan T, Greene KL, Feng F, Carroll PR, Hope TA. Single-Center Prospective Evaluation of 68Ga-PSMA-11 PET in Biochemical Recurrence of Prostate Cancer. AJR Am J Roentgenol. 2019 Apr 30; 1-8.
Seo Y, Khalighi MM, Wangerin KA, Deller TW, Wang YH, Jivan S, Kohi MP, Aggarwal R, Flavell RR, Behr SC, Evans MJ. Quantitative and Qualitative Improvement of Low-Count [68Ga]Citrate and [90Y]Microspheres PET Image Reconstructions Using Block Sequential Regularized Expectation Maximization Algorithm. Mol Imaging Biol. 2019 Apr 15.
Fendler WP, Calais J, Eiber M, Flavell RR, Mishoe A, Feng FY, Nguyen HG, Reiter RE, Rettig MB, Okamoto S, Emmett L, Zacho HD, Ilhan H, Wetter A, Rischpler C, Schoder H, Burger IA, Gartmann J, Smith R, Small EJ, Slavik R, Carroll PR, Herrmann K, Czernin J, Hope TA. Assessment of 68Ga-PSMA-11 PET Accuracy in Localizing Recurrent Prostate Cancer: A Prospective Single-Arm Clinical Trial. JAMA Oncol. 2019 Mar 28.
Perez PM, Flavell RR, Kelley RK, Umetsu S, Behr SC. Heterogeneous Uptake of 18F-FDG and 68Ga-PSMA-11 in Hepatocellular Carcinoma. Clin Nucl Med. 2019 Mar; 44(3):e133-e135.
Bok R, Lee J, Sriram R, Keshari K, Sukumar S, Daneshmandi S, Korenchan DE, Flavell RR, Vigneron DB, Kurhanewicz J, Seth P. The Role of Lactate Metabolism in Prostate Cancer Progression and Metastases Revealed by Dual-Agent Hyperpolarized 13C MRSI. Cancers (Basel). 2019 Feb 22; 11(2).
Perez PM, Hope TA, Behr SC, van Zante A, Small EJ, Flavell RR. Intertumoral Heterogeneity of 18F-FDG and 68Ga-PSMA Uptake in Prostate Cancer Pulmonary Metastases. Clin Nucl Med. 2019 Jan; 44(1):e28-e32.
Behr SC, Aggarwal R, Van Brocklin HF, Flavell RR, Geo K, Small EJ, Blecha J, Jivan S, Hope TA, Simko JP, Kurhanewicz J, Noworolski SM, Korn NJ, De Los Santos R, Cooperberg MR, Carroll PR, Nguyen HG, Greene KL, Langton-Webster B, Berkman CE, Seo Y. First-in-Human Phase I study of CTT1057, a Novel 18F Labeled Imaging Agent with Phosphoramidate Core Targeting Prostate Specific Membrane Antigen in Prostate Cancer. J Nucl Med. 2018 Nov 21.
Ding Y, Sohn JH, Kawczynski MG, Trivedi H, Harnish R, Jenkins NW, Lituiev D, Copeland TP, Aboian MS, Mari Aparici C, Behr SC, Flavell RR, Huang SY, Zalocusky KA, Nardo L, Seo Y, Hawkins RA, Hernandez Pampaloni M, Hadley D, Franc BL. A Deep Learning Model to Predict a Diagnosis of Alzheimer Disease by Using 18F-FDG PET of the Brain. Radiology. 2019 Feb; 290(2):456-464.
Villanueva-Meyer JE, Magill ST, Lee JC, Umetsu SE, Flavell RR. Detection of Metastatic Meningioma to the Liver Using 68Ga-DOTA-Octreotate PET/CT. Clin Nucl Med. 2018 Sep; 43(9):e338-e340.
Qin H, Carroll VN, Sriram R, Villanueva-Meyer JE, von Morze C, Wang ZJ, Mutch CA, Keshari KR, Flavell RR, Kurhanewicz J, Wilson DM. Imaging glutathione depletion in the rat brain using ascorbate-derived hyperpolarized MR and PET probes. Sci Rep. 2018 May 21; 8(1):7928.
Taglang C, Korenchan DE, von Morze C, Yu J, Najac C, Wang S, Blecha JE, Subramaniam S, Bok R, VanBrocklin HF, Vigneron DB, Ronen SM, Sriram R, Kurhanewicz J, Wilson DM, Flavell RR. Late-stage deuteration of 13C-enriched substrates for T1 prolongation in hyperpolarized 13C MRI. Chem Commun (Camb). 2018 May 17; 54(41):5233-5236.
Mutch CA, Ordonez AA, Qin H, Parker M, Bambarger LE, Villanueva-Meyer JE, Blecha J, Carroll V, Taglang C, Flavell R, Sriram R, VanBrocklin H, Rosenberg O, Ohliger MA, Jain SK, Neumann KD, Wilson DM. [11C]Para-Aminobenzoic Acid: A Positron Emission Tomography Tracer Targeting Bacteria-Specific Metabolism. ACS Infect Dis. 2018 Jul 13; 4(7):1067-1072.
Ng QKT, Sethi P, Saunders TA, Pampaloni MH, Flavell RR. Discordant Findings on 18F-NaF and 99mTc-HDP Bone Scans in a Patient With ATTR Cardiac Amyloidosis. Clin Nucl Med. 2018 Mar; 43(3):e89-e92.
Pittman S, Sethi P, Flavell RR, Pampaloni MH. Cardiac Fibroma: An Uncommon Cause of a Fixed Defect on Myocardial Perfusion Imaging. Clin Nucl Med. 2018 Feb; 43(2):e56-e58.
von Morze C, Ohliger MA, Marco-Rius I, Wilson DM, Flavell RR, Pearce D, Vigneron DB, Kurhanewicz J, Wang ZJ. Direct assessment of renal mitochondrial redox state using hyperpolarized 13 C-acetoacetate. Magn Reson Med. 2018 04; 79(4):1862-1869.
Pittman S, Sethi P, Flavell RR, De Marco T, Hernandez Pampaloni M. Abnormal pulmonary 18F-florbetapir uptake in a patient evaluated for recurrent cardiac amyloidosis following orthotopic heart transplant. J Nucl Cardiol. 2018 Oct; 25(5):1865-1868.
Neumann KD, Villanueva-Meyer JE, Mutch CA, Flavell RR, Blecha JE, Kwak T, Sriram R, VanBrocklin HF, Rosenberg OS, Ohliger MA, Wilson DM. Imaging Active Infection in vivo Using D-Amino Acid Derived PET Radiotracers. Sci Rep. 2017 08 11; 7(1):7903.
Neumann K, Flavell R, Wilson DM. Exploring Metabolism In Vivo Using Endogenous 11C Metabolic Tracers. Semin Nucl Med. 2017 09; 47(5):461-473.
Korenchan DE, Taglang C, von Morze C, Blecha JE, Gordon JW, Sriram R, Larson PEZ, Vigneron DB, VanBrocklin HF, Kurhanewicz J, Wilson DM, Flavell RR. Dicarboxylic acids as pH sensors for hyperpolarized 13C magnetic resonance spectroscopic imaging. Analyst. 2017 May 02; 142(9):1429-1433.
Salimy MS, Parwani PJ, Mukai K, Pampaloni MH, Flavell RR. Abnormal 18F-FDG and 82Rb PET Findings in Chagas Heart Disease. Clin Nucl Med. 2017 May; 42(5):e265-e268.
Lawhn-Heath C, Flavell RR, Glastonbury C, Hope TA, Behr SC. Incidental Detection of Head and Neck Squamous Cell Carcinoma on 68Ga-PSMA-11 PET/CT. Clin Nucl Med. 2017 Apr; 42(4):e218-e220.
Behr SC, Mollard BJ, Yang J, Flavell RR, Hawkins RA, Seo Y. Effect of Time-of-Flight and Regularized Reconstructions on Quantitative Measurements and Qualitative Assessments in Newly Diagnosed Prostate Cancer With 18F-Fluorocholine Dual Time Point PET/MRI. Mol Imaging. 2017 Jan-Dec; 16:1536012117736703.
Flavell RR, Behr SC, Mabray MC, Hernandez-Pampaloni M, Naeger DM. Detecting Pulmonary Nodules in Lung Cancer Patients Using Whole Body FDG PET/CT, High-resolution Lung Reformat of FDG PET/CT, or Diagnostic Breath Hold Chest CT. Acad Radiol. 2016 09; 23(9):1123-9.
Liu W, Truillet C, Flavell RR, Brewer TF, Evans MJ, Wilson DM, Chang CJ. A reactivity-based [18F]FDG probe for in vivo formaldehyde imaging using positron emission tomography. Chem Sci. 2016 Aug 01; 7(8):5503-5507.
Carroll VN, Truillet C, Shen B, Flavell RR, Shao X, Evans MJ, VanBrocklin HF, Scott PJ, Chin FT, Wilson DM. [(11)C]Ascorbic and [(11)C]dehydroascorbic acid, an endogenous redox pair for sensing reactive oxygen species using positron emission tomography. Chem Commun (Camb). 2016 Apr 07; 52(27):4888-90.
Korenchan DE, Flavell RR, Baligand C, Sriram R, Neumann K, Sukumar S, VanBrocklin H, Vigneron DB, Wilson DM, Kurhanewicz J. Dynamic nuclear polarization of biocompatible (13)C-enriched carbonates for in vivo pH imaging. Chem Commun (Camb). 2016 Feb 18; 52(14):3030-3.
Flavell RR, Naeger DM, Aparici CM, Hawkins RA, Pampaloni MH, Behr SC. Malignancies with Low Fluorodeoxyglucose Uptake at PET/CT: Pitfalls and Prognostic Importance: Resident and Fellow Education Feature. Radiographics. 2016 Jan-Feb; 36(1):293-4.
Flavell RR, Truillet C, Regan MK, Ganguly T, Blecha JE, Kurhanewicz J, VanBrocklin HF, Keshari KR, Chang CJ, Evans MJ, Wilson DM. Caged [(18)F]FDG Glycosylamines for Imaging Acidic Tumor Microenvironments Using Positron Emission Tomography. Bioconjug Chem. 2016 Jan 20; 27(1):170-8.
Flavell RR, von Morze C, Blecha JE, Korenchan DE, Van Criekinge M, Sriram R, Gordon JW, Chen HY, Subramaniam S, Bok RA, Wang ZJ, Vigneron DB, Larson PE, Kurhanewicz J, Wilson DM. Application of Good's buffers to pH imaging using hyperpolarized (13)C MRI. Chem Commun (Camb). 2015 Sep 25; 51(74):14119-22.
Mabray MC, Behr SC, Naeger DM, Flavell RR, Glastonbury CM. Predictors of pathologic outcome of focal FDG uptake in the parotid gland identified on whole-body FDG PET imaging. Clin Imaging. 2015 Nov-Dec; 39(6):1073-9.
Flavell RR, Westphalen AC, Liang C, Sotto CC, Noworolski SM, Vigneron DB, Wang ZJ, Kurhanewicz J. Abnormal findings on multiparametric prostate magnetic resonance imaging predict subsequent biopsy upgrade in patients with low risk prostate cancer managed with active surveillance. Abdom Imaging. 2014 Oct; 39(5):1027-35.
Flavell RR, Behr SC, Brunsing RL, Naeger DM, Pampaloni MH. The incidence of pulmonary embolism and associated FDG-PET findings in IV contrast-enhanced PET/CT. Acad Radiol. 2014 Jun; 21(6):718-25.
Ceccarini G, Flavell RR, Butelman ER, Synan M, Willnow TE, Bar-Dagan M, Goldsmith SJ, Kreek MJ, Kothari P, Vallabhajosula S, Muir TW, Friedman JM. PET imaging of leptin biodistribution and metabolism in rodents and primates. Cell Metab. 2009 Aug; 10(2):148-59.
Flavell RR, Muir TW. Expressed protein ligation (EPL) in the study of signal transduction, ion conduction, and chromatin biology. Acc Chem Res. 2009 Jan 20; 42(1):107-16.
Flavell RR, Kothari P, Bar-Dagan M, Synan M, Vallabhajosula S, Friedman JM, Muir TW, Ceccarini G. Site-specific (18)F-labeling of the protein hormone leptin using a general two-step ligation procedure. J Am Chem Soc. 2008 Jul 16; 130(28):9106-12.
Flavell RR, Huse M, Goger M, Trester-Zedlitz M, Kuriyan J, Muir TW. Efficient semisynthesis of a tetraphosphorylated analogue of the Type I TGFbeta receptor. Org Lett. 2002 Jan 24; 4(2):165-8.