Robert Flavell, MD, PhD

Assistant Professor
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

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

Publications

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 Aug 11; 7(1):7903.
Neumann K, Flavell R, Wilson DM. Exploring Metabolism In Vivo Using Endogenous 11C Metabolic Tracers. Semin Nucl Med. 2017 Sep; 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.
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 Sep; 23(9):1123-9.
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.