University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Robert Flavell, MD, PhD

Robert Flavell, MD, PhD

Assistant Professor in Residence, Department of Radiology and Biomedical Imaging, UCSF

Cancer Center Program Memberships

Prostate Cancer

Research Summary

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.

Education

Wesleyan University, Middletown, CT, B.A., 1996-2000, Mathematics and chemistry
The Rockefeller University, New York, NY, laboratory of Dr. Tom W. Muir, PhD, 2002 - 2010, Peptide and protein chemistry, radiolabeling methods, and PET imaging
Weill Cornell Medical College, New York, NY, MD, 2002 - 2010, Medicine
Memorial Sloan-Kettering Cancer Center, 2010 - 2011, Transitional year intern
Dept of Radiology, UCSF Medical Center, San Francisco, CA, 2011 - 2015, Diagnostic radiology residency
Dept of Radiology, UCSF Medical Center, San Francisco, CA 2015 - 2016, Nuclear medicine fellowship

Honors & Awards

  • 2000
    Honors for undergraduate thesis in chemistry, Wesleyan University, Middletown, CT
  • 2013
    Introduction to Academic Radiology Program, American Roentgen Ray Society
  • 2014
    Certificate of Merit, 2014 Radiology Society of North America meeting
  • 2014
    University of California, San Francisco catalyst program consultation award
  • 2015
    Radiology Society of North America, Roentgen Resident Research award
  • 2015
    Association of University Radiologists Research Scholar Program
  • 2015
    Certificate of Merit, 2015 Radiology Society of North America Meeting
  • 2016
    Runner up, Surbeck Scholar’s Award, University of California, San Francisco

Selected Publications

  1. Huang Y, Zhao N, Wang YH, Truillet C, Wei J, Parker MFL, Blecha JE, Drake CR, VanBrocklin HF, Ruiz DG, Jacobson MP, Aggarwal R, Behr SC, Flavell RR, Wilson DM, Seo Y, Evans MJ. The synthesis and structural requirements for measuring glucocorticoid receptor expression in vivo with (±)-11C-YJH08 PET. J Nucl Med. 2020 Sep 04.
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  2. Murthy V, Smith RL, Tao DH, Lawhn-Heath CA, Korenchan DE, Larson PEZ, Flavell RR, Hope TA. 68Ga-PSMA-11 PET/MRI: determining ideal acquisition times to reduce noise and increase image quality. EJNMMI Phys. 2020 Aug 26; 7(1):54.
    View on PubMed
  3. Wei J, Wang YH, Lee CY, Truillet C, Oh DY, Xu Y, Ruggero D, Flavell RR, VanBrocklin HF, Seo Y, Craik CS, Fong L, Wang CI, Evans MJ. An Analysis of Isoclonal Antibody Formats Suggests a Role for Measuring PD-L1 with Low Molecular Weight PET Radiotracers. Mol Imaging Biol. 2020 Aug 19.
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  4. Polvoy I, Flavell RR, Ohliger M, Rosenberg O, Wilson DM. Nuclear imaging of bacterial infection- state of the art and future directions. J Nucl Med. 2020 Aug 06.
    View on PubMed
  5. Flavell RR, Evans MJ, Villanueva-Meyer JE, Yom SS. Understanding Response to Immunotherapy Using Standard of Care and Experimental Imaging Approaches. Int J Radiat Oncol Biol Phys. 2020 Sep 01; 108(1):242-257.
    View on PubMed
  6. Parker MFL, Flavell RR, Luu JM, Rosenberg OS, Ohliger MA, Wilson DM. Small Molecule Sensors Targeting the Bacterial Cell Wall. ACS Infect Dis. 2020 07 10; 6(7):1587-1598.
    View on PubMed
  7. Fendler WP, Ferdinandus J, Czernin J, Eiber M, Flavell RR, Behr SC, Wu IK, Lawhn-Heath C, Pampaloni MH, Reiter RE, Rettig MB, Gartmann J, Murthy V, Slavik R, Carroll PR, Herrmann K, Calais J, Hope TA. Impact of 68Ga-PSMA-11 PET on the Management of recurrent Prostate Cancer in a Prospective Single-Arm Clinical Trial. J Nucl Med. 2020 May 01.
    View on PubMed
  8. Chiu LW, Lawhn-Heath C, Behr S, Juarez R, Perez PM, Lobach I, Bucknor MD, Hope TA, Flavell RR. Factors predicting metastatic disease in 68Ga-PSMA-11 PET positive osseous lesions in prostate cancer. J Nucl Med. 2020 Apr 17.
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  9. Kalita M, Parker MFL, Luu JM, Stewart MN, Blecha JE, VanBrocklin HF, Evans MJ, Flavell RR, Rosenberg OS, Ohliger MA, Wilson DM. Arabinofuranose-derived positron-emission tomography radiotracers for detection of pathogenic microorganisms. J Labelled Comp Radiopharm. 2020 May 15; 63(5):231-239.
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  10. Parker MFL, Luu JM, Schulte B, Huynh TL, Stewart MN, Sriram R, Yu MA, Jivan S, Turnbaugh PJ, Flavell RR, Rosenberg OS, Ohliger MA, Wilson DM. Sensing Living Bacteria in Vivo Using d-Alanine-Derived 11C Radiotracers. ACS Cent Sci. 2020 Feb 26; 6(2):155-165.
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  11. 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. 2020 02; 22(1):208-216.
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  12. Lawhn-Heath C, Flavell RR, Chuang EY, Liu C. Failure of iodine uptake in microscopic pulmonary metastases after recombinant human thyroid-stimulating hormone stimulation. World J Nucl Med. 2020 Jan-Mar; 19(1):61-64.
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  13. Stewart MN, Parker MFL, Jivan S, Luu JM, Huynh TL, Schulte B, Seo Y, Blecha JE, Villanueva-Meyer JE, Flavell RR, VanBrocklin HF, Ohliger MA, Rosenberg O, Wilson DM. High Enantiomeric Excess In-Loop Synthesis of d-[methyl-11C]Methionine for Use as a Diagnostic Positron Emission Tomography Radiotracer in Bacterial Infection. ACS Infect Dis. 2020 01 10; 6(1):43-49.
    View on PubMed
  14. Georgios Batsios, Pavithra Viswanath, Peng Cao, Celine Taglang, Elavarasan Subramani, Robert Flavell, Peder Larson, Sabrina Ronen. CBMT-08. IN VIVO EVALUATION OF PENTOSE PHOSPHATE PATHWAY ACTIVITY IN ORTHOTOPIC GLIOMA USING HYPERPOLARIZED d-[1-13C]GLUCONOLACTONE. Neuro-Oncology. 2019 Nov 11; 21(Supplement_6):vi34-vi34.
    View on PubMed
  15. Korenchan DE, Bok R, Sriram R, Liu K, Santos RD, Qin H, Lobach I, Korn N, Wilson DM, Kurhanewicz J, Flavell RR. Hyperpolarized in vivo pH imaging reveals grade-dependent acidification in prostate cancer. Oncotarget. 2019 Oct 22; 10(58):6096-6110.
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  16. Wang S, Korenchan DE, Perez PM, Taglang C, Hayes TR, Sriram R, Bok R, Hong AS, Wu Y, Li H, Wang Z, Kurhanewicz J, Wilson DM, Flavell RR. Amino Acid-Derived Sensors for Specific Zn2+ Detection Using Hyperpolarized 13 C Magnetic Resonance Spectroscopy. Chemistry. 2019 Sep 12; 25(51):11842-11846.
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  17. Wang S, Blaha C, Santos R, Huynh T, Hayes TR, Beckford-Vera DR, Blecha JE, Hong AS, Fogarty M, Hope TA, Raleigh DR, Wilson DM, Evans MJ, VanBrocklin HF, Ozawa T, Flavell RR. Synthesis and Initial Biological Evaluation of Boron-Containing Prostate-Specific Membrane Antigen Ligands for Treatment of Prostate Cancer Using Boron Neutron Capture Therapy. Mol Pharm. 2019 09 03; 16(9):3831-3841.
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  18. Korenchan DE, Flavell RR. Spatiotemporal pH Heterogeneity as a Promoter of Cancer Progression and Therapeutic Resistance. Cancers (Basel). 2019 Jul 20; 11(7).
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  19. 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 Jun 01; 5(6):856-863.
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  20. 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 09; 82(3):959-972.
    View on PubMed

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