Molecular Imaging Lab (Flavell Lab)

The overall goal of the molecular imaging lab (Flavell Lab) is the development of new molecular imaging and theranostic probes for better detection and therapy in patients with cancer. We focus on modalities including positron emission tomography (PET), radionuclide therapies, and hyperpolarized 13C magnetic resonance imaging. Members of the laboratory integrate new chemistry, chemical biology, imaging, and clinical methods, with the ultimate goal of developing new methodologies to help improve patient care.

molecular imaging probes

Research Projects

Project 1

Molecular imaging of the tumor microenvironment using positron emission tomography and hyperpolarized 13C methods

Molecular imaging of tumor pH using hyperpolarized 13C probes

In this project, new molecular imaging probes are utilized as biosensors to detect changes in the microenvironment such as changes in pH or metal concentration. In the example above, a novel hyperpolarized 13C imaging probe, diethylmalonic acid, was used to accurately image pH.

Citations:

  • 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. doi: 10.1039/c5cc05348j. PubMed PMID: 26257040; PubMed Central PMCID: PMC4854286. https://pubs.rsc.org/en/content/articlehtml/2015/cc/c5cc05348j
  • 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 (13)C magnetic resonance spectroscopic imaging. Analyst. 2017 May 2;142(9):1429-1433. doi: 10.1039/c7an00076f. PubMed PMID: 28322385; PubMed Central PMCID: PMC5462110. https://pubs.rsc.org/en/content/articlehtml/2017/an/c7an00076f
  • Wang S, Korenchan DE, Perez PM, et al. Amino Acid-Derived Sensors for Specific Zn2+Detection Using Hyperpolarized 13 C Magnetic Resonance Spectroscopy. Chemistry. 2019;25(51):11842-11846. doi:10.1002/chem.201902771 https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/chem.201902771
  • 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. doi: 10.1021/acs.bioconjchem.5b00584. Epub 2015 Dec 22. PubMed PMID: 26649808; PubMed Central PMCID: PMC4854293. https://pubs.acs.org/doi/full/10.1021/acs.bioconjchem.5b00584

Project 2

Molecular imaging of tumor pH for better risk stratification in prostate cancer

Molecular imaging of tumor pH in prostate cancer

In this project, hyperpolarized 13C MRI probes such as bicarbonate, produced via the glycerol carbonate method, are applied to high spatial resolution imaging of tumor pH. The resulting pH maps can be used to discriminate between low and high grade cancers in mouse models.

Citations:

Project 3

Development of theranostic methods for imaging and treatment of cancer

theranostic methods for imaging and treatment of cancer

In this project, we develop new methods to enable both imaging and therapy of cancer using theranostic probes. Imaging is typically done using positron emission tomography, and therapy may be done with radionuclide or neutron capture therapy. In this example, a new immunoPET agent, [89Zr]DFO-YS5 is imaged in a dual tumor prostate cancer model, enabling detection of 22Rv1 and DU145 tumors.

Citations:

Wang, S., et al. (2019). "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 16(9): 3831-3841. https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.9b00464

Project 4

Translational and clinical nuclear medicine and molecular imaging research

Translational and clinical nuclear medicine

In this project, findings in the laboratory are translated into the clinic. We also conduct prospective and retrospective clinical studies of new molecular imaging and therapy agents. In this, example, we conducted a retrospective analysis of findings which are associated with true positive metastatic disease on prostate specific antigen (PSMA) PET.

Citations:

People

Robert Flavell, MD, PhDRobert Flavell, MD, PhD
Principal Investigator
Assistant Professor in Residence

 

 

 


Niranjan MeherNiranjan Meher
Postdoctoral Fellow
[email protected]

 

 

 


Changhua Mu, Postdoc, Flavell labChanghua Mu
Postdoctoral Fellow
[email protected]

 


 


Paola PerezPaola Perez Rivera
UCSF Medical Student
[email protected]

 

 

 


Sinan Wang, PostdocSinan Wang
Postdoctoral Fellow
[email protected]

 

 

 


Mayuri Jayaraman
UC Berkeley Student

 

 

 


Alumni

  • Andrew Hong, UC Berkeley Student
  • David Korenchan, Postdoctoral Fellow
  • Henry Li, MSBI Graduate Student
  • Kristina Liu, Junior Specialist
  • Celine Taglang, Postdoctoral Fellow
  • Walter Zhao, MSBI Graduate Student
  • Justin Yu, MSBI Graduate Student

Opportunities

We are actively recruiting postdoctoral fellows and graduate students (pdf) with interests in molecular imaging, positron emission tomography, chemistry and radiochemistry, and hyperpolarized 13C MRI. 

Please contact Dr. Flavell with inquiries: [email protected]

News

July 2020

Dr. Flavell published a review article on the imaging of response to immunotherapy in International Journal of Radiation Oncology *Biology* Physics.

Congrats to our collaborator, Dr. Parker from Dave Wilson’s lab, on his review article on “Small molecule sensors targeting the bacterial cell wall”. 

June 2020

Congrats to Le Wen Chiu on her article in the Journal of Nuclear Medicine on the detection of osseous metastatic disease on PSMA PET!

May 2020

Congrats to Niranjan and Changhua for being awarded Seed Grants from the UCSF Department of Radiology and Biomedical Imaging

Our collaborator, Dr. Hope, published a manuscript in the Journal of Nuclear Medicine entitled “Impact of 68Ga-PSMA-11 PET on the Management of Recurrent Porstate Cancer in a Prospective Single-Arm Clinical Trial”.

Congrats to our collaborator Mausam Kalita from Dave Wilson’s lab on his publication entitled “Arabinofuranose-derived positron-emission tomography radiotracers for detection of pathogenic microorganisms”.

March 2020

Dr. Flavell was awarded a Translational Science Award from the Department of Defense Prostate Cancer Research Program

February 2020

Sinan and Rob both lectured at the UCSF Precision Imaging of Cancer and Therapy Retreat, and Niranjan presented a poster.

Congratulations to Dr. Parker from Dave Wilson’s lab on his publication in ACS Central Science, entitled “Sensing Living Bacteria in vivo using d-Alanine-Derived 11C Radiotracers".

December 2019

Dr. Flavell was awarded a grant from University of California Precision Imaging of Cancer and Therapy, entitled “Clinical Translation of a Theranostic Immuno-PET Agent Targeting CD46 in Men with Castration Resistant Prostate Cancer”.

November 2019

Our collaborator Dr. Stewart published a paper entitled “High Enantiomeric Excess In-Loop Synthesis of d-[methyl-11C]Methionine for Use as a Diagnostic Positron Emission Tomography Radiotracer in Bacterial Infection” in ACS Infectious Disease.

October 2019

Congrats to Dave Korenchan on publication of his manuscript entitled “Hyperpolarized in vivo pH imaging reveals grade-dependent acidification in prostate cancer”.

July 2019

Congrats to Sinan Wang on publication of his new article, "Amino Acid-Derived Sensors for Specific Zn2+ Detection Using Hyperpolarized 13C Magnetic Resonance Spectroscopy", in Chemstry, a European Journal.

Congrats to Dave Korenchan on publishing a well written review summarizing recent developments in molecular imaging of interstitial pH in Cancers, entitled "Spatiotemporal pH Heterogeneity as a Promoter of Cancer Progression and Therapeutic Resistances."

June 2019

Congrats to Sinan on receiving the PBBR Postdoc independent research grant and Radiology Department Seed Grant!

May 2019

Congrats Dave Korenchan on his paper entitled “Using bidirectional chemical exchange for improved hyperpolarized 13C bicarbonate pH imaging” in Magnetic Resonance in Medicine.

March 2019

Dr. Flavell presented at the Society of Abdominal Radiology on: ”SAR 2017 Howard S. Stern Research Grant Report: Imaging of Zinc Metabolism Using Hyperpolarized 13C Magnetic Resonance Imaging" (pdf).

Flavell lab was well represented at the 2019 UCSF HMTRC with a poster presentation from Celine Taglang on “Imaging Tissue pH Using Chemical Shift-based Hyperpolarized 13C MRI Probes”, and Dave Korenchan and Sinan Wang running the chemical probes workshop.

Congrats Andrew Hong for receiving the Rose Hills Summer Undergraduate Research Fellowship!

January 2019

Multiple presentations from Flavell lab at the precision imaging of cancer and therapy (PICT) retreat from Celine on “Imaging Tissue pH Using Chemical Shift-based Hyperpolarized 13C MRI Probes”, and Sinan on “Synthesis of borane-containing PSMA inhibitors and their biological evaluation for BNCT treatment of prostate cancer”

Dr. Flavell presented at the Northern California Health Physics Society on “Molecular Imaging Tools to Understand Cancer Progression” 

Dr. Flavell was awarded a research grant on “Risk stratification in prostate cancer using pH imaging” from the University of California Cancer Research Coordinating Committee.

October 2018

Flavell lab was well represented at the UCSF radiology research symposium with presentations including Celine Taglang’s ”Imaging tissue pH using chemical shift-based hyperpolarized 13C MRI probes”, Sinan Wang’s entitled “Development and validation of new hyperpolarized 13C magnetic resonance imaging probes targeting zinc metabolism”, Dave Korenchan’s entitled “Hyperpolarized In vivo pH Imaging Reveals Grade-Dependent Acidification in Prostate Cancer”, and Kristin Liu’s entitled “Towards Clinical Hyperpolarized 13C pH Imaging Using a New Bicarbonate Precursor”

Dr. Flavell presented at the UCSF prostate cancer program retreat on “Towards therapy of prostate cancer using boronated PSMA neutron capture therapy”

Dr. Flavell presented at the Prostate cancer foundation retreat on “Detection of aggressive prostate cancer through pH imaging using hyperpolarized 13C magnetic resonance spectroscopy”

September 2018

Sinan Wang presented a poster entitled “Development and validation of new hyperpolarized 13C magnetic resonance imaging probes targeting zinc metabolism” at the World Molecular Imaging Conference

August 2018

Andrew Hong presented his summer research project at the UC Berkeley SURF conference, entitled “Hyperpolarized Magnetic Resonance Zinc Probes for Prostate Cancer Detection and Risk Stratification.”

June 2018

Congratulations to Dave Korenchan for his poster presentations entitled "Hyperpolarized In vivo pH Imaging Reveals Grade-Dependent Interstitial Acidification” and "Mitigating Chemical Exchange Effects in Advanced Pulse Sequences for pH Imaging with Hyperpolarized [13C]bicarbonate”, and Celine for her poster presentation entitled: "Late-stage deuteration of 13C-enriched substrates for T1 prolongation in hyperpolarized 13C MRI” at the 2018 International Society of Magnetic Resonance in Medicine meeting in Paris.

Congratulations to Paola Perez Rivera for receiving the Research Initiative to Promote Diversity in Radiology (RIDR) summer fellowship! 

Congratulations to Andrew Hong for receiving the SURF Rose Hills Independent Fellowship!

May 2018

Congratulations Celine Taglang on publication of her new article, "Late-stage deuteration of 13C-enriched substrates for T1 prolongation in hyperpolarized 13C MRI” in Chemical Communications"

Dr. Flavell was awarded an NIH R21 grant entitled: “Application of hyperpolarized 13C interstitial pH imaging to risk stratification in prostate cancer

November 2017

Dr. Flavell was Awarded a UCSF Prostate Cancer Program New Directions in Prostate Cancer Research Award.

Dr. Flavell gave a lecture at the Osher mini medical school for the public entitled “Cancer Detection and Treatment through Molecular Imaging: Theranostics at UCSF.” The lecture can be viewed on the following website: https://www.uctv.tv/shows/Cancer-Detection-and-Treatment-through-Molecular-Imaging-Theranostics-at-UCSF-32929

https://osherminimed.ucsf.edu/sites/osherminimed.ucsf.edu/files/wysiwyg/
Flavell_tomography.pdf

Congratulations to Dave Korenchan on an excellent poster presentation at the UCSF Prostate Cancer Program retreat!

October 2017

Congrats to Celine Taglang, Dave Korenchan and Sinan Wang on excellent oral presentations at the Precision Imaging in Cancer Therapy (PICT) symposium, and poster presentations at the UCSF Department of Radiology Research Symposium!
http://cancer.ucsf.edu/events/2017/10/04/precision-imaging-of-cancer-and-therapy-annual-retreat.8488

July 2017

Congratulations to our master’s degree graduates Justin Yu and Henry Li for their excellent thesis and presentations! Justin presented on “Optimization of pH imaging methodology for hyperpolarized 13C MRI” and Henry presented on “Detection of prostate cancer through molecular imaging of zinc using hyperpolarized 13C MRI”.

June 2017

Dr. Flavell received the Prostate Cancer Foundation Young Investigator Award.

April 2017 Congratulations to Dave Korenchan for his Magna Cum Laude award at the International Society of Magnetic Resonance in Medicine meeting for his presentation entitled "Chemical Shift Imaging of pH with Hyperpolarized [2-13C,D10] Diethylmalonic Acid", and “Hyperpolarization Methods & Equipment for Targeting Biological Mechanisms Study Group Abstract Award for best oral presentation”.

March 2017
Dr. Flavell was awarded the Howard S. Stern research award by the Society of Abdominal Radiology for his proposal entitled “Imaging of Zn metabolism using hyperpolarized 13C magnetic resonance imaging in prostate cancer".

February 2017
Dr. Robert Flavell was awarded an American Cancer Society individual research grant.

January 2017
Congratulations to Celine Taglang for being awarded a Department of Defense Postdoctoral Early Investigator Research Award.

September 2016
Dr. Robert Flavell was awarded a Department of Defense Physician Research Training Grant, entitled “Detection of aggressive prostate tumors using novel PET and hyperpolarized 13C probes targeting interstitial acidity.

Publications

Featured Publications

Chiu, L. W., et al. (2020). "Factors predicting metastatic disease in (68)Ga-PSMA-11 PET positive osseous lesions in prostate cancer." J Nucl Med.

Wang, S., et al. (2019). "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 16(9): 3831-3841.

Korenchan, D. E., et al. (2019). "Hyperpolarized in vivo pH imaging reveals grade-dependent acidification in prostate cancer." Oncotarget 10(58): 6096-6110.

Korenchan, D. E. and R. R. Flavell (2019). "Spatiotemporal pH Heterogeneity as a Promoter of Cancer Progression and Therapeutic Resistance." Cancers (Basel) 11(7).

Wang S, Korenchan DE, Perez PM, et al. Amino Acid-Derived Sensors for Specific Zn2+Detection Using Hyperpolarized 13 C Magnetic Resonance Spectroscopy. Chemistry. 2019;25(51):11842-11846. doi:10.1002/chem.201902771, https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/chem.201902771

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 [13C]bicarbonate pH imaging. Magn Reson Med. 2019 May 3. doi: 10.1002/mrm.27780. [Epub ahead of print] PubMed PMID: 31050049.

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 T(1) prolongation in hyperpolarized 13C MRI. Chem Commun (Camb). 2018 May 17;54(41):5233-5236. doi: 10.1039/c8cc02246a. PubMed PMID: 29726563; PubMed Central PMCID: PMC6054790.

Korenchan DE, Taglang C, von Morze C, Blecha JE, Gordon JW, Sriram R, Larson PE, Vigneron DB, VanBrocklin HF, Kurhanewicz J, Wilson DM, Flavell RR. Dicarboxylic acids as pH sensors for hyperpolarized 13C magnetic resonance spectroscopic imaging. Analyst, 2017. DOI: 10.1039/C7AN00076F 

Flavell R.R.; Westphalen, A.C.; Liang, C.; Sotto, C.C.; Noworolski, S.M.; Vigneron, D.B.; Wang, Z.J.; Kurhanewicz, J. Abnormal findings on multiparametric prostate magnetic resonance imaging predict disease progression in patients with low risk prostate cancer managed with active surveillance, Abdom Imaging. 2014 Oct; 39(5):1027-35.

Flavell, R.R., Korenchan, D; von Morze, C; Van Criekinge, M; Sriram, R.; Gordon, J.; Subramaniam S.; Bok, R.; Blecha, J.; Vigneron, D.; Keshari K.; Larson, P.; Kurhanewicz J.; Wilson, D.M.  Application of Good’s buffers to pH imaging using hyperpolarized 13C-MRI Chem. Comm. 2015. 51, 14119-22.

Flavell R.R., Truillet C., Regan M.K., Ganguly T., Blecha J.E., Kurhanewicz J., VanBrocklin H.F., Keshari K.R., Chang C.J., Evans M.J., Wilson D.M. Caged [18F]FDG glycosylamines for imaging acidic tumor microenvironment using positron emission tomography, Bioconjugate chem. 2016, 27, 170-8. 

Flavell, R.R., Naeger, D.M., Mari Aparici, C., Hawkins, R.A., Pampaloni, M.H., Behr, S.C. Low FDG avidity malignancy on PET/CT: Pitfalls and Prognostic Significance Radiographics 2016, 36, 293-4.

Korenchan D.E., Flavell R.R., Baligand C., Sriram R., Neumann K., Sukumar S., VanBrocklin H., Vigneron D.B., Wilson D.M., Kurhanewicz J., Dynamic nuclear polarization of biocompatible 13C-enriched carbonates for in vivo pH imaging. Chem Comm., 2016, 52, 3030-3.

Flavell R.R., Wilson D.M., Behr S.C., Recent developments in combined PET/MRI. Curr. Radiol. Rep., 2016, 4(5) 1-10. 

Carroll V., Truillet C., Shen B., Flavell R.R., Shao X, Evans M.J., VanBrocklin H.F., Scott P., Chin F., Wilson D.M. [11C]Ascorbic and [11C]Dehydroascorbic acid, an endogenous redox pair for sensing reactive oxygen species using positron emission tomography. Chem. Comm. 2016, 52, 4888-90.

Flavell R.R., Behr S.C., Mabray M.C., Henandez-Pampaloni M., Naeger D.M., 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, in press.

Liu W., Truillet C., Flavell R.R., Brewer T.F., Evans M.J., Wilson D.M., Chang C.J. A reactivity based [18F]FDG probe for in vivo formaldehyde imaging using positron emission tomography. Chem. Sci. 2016, 7, 5503-7.

Complete list of publications:

https://www.ncbi.nlm.nih.gov/myncbi/browse/collection/46224495/?sort=date&direction=ascending

Research gate site:

https://www.researchgate.net/profile/Robert_Flavell?

Director of Molecular Imaging Lab

Assistant Professor
Chief, Molecular Imaging & Therapeutics
Asst Professor in Residence