Michael Evans' Lab

Translational research at the interface of chemical biology and nuclear medicine

The scientific premise of the Evans lab is that there are natural, and largely untapped synergies between chemical biology and nuclear medicine.  For instance, molecular profiling technologies developed, refined, and applied by chemical biologists (e.g. proteomics, metabolomics) routinely glean biological discoveries that can be exploited by the nuclear medicine community to improve the detection and treatment of major public health challenges.  Conversely, researchers in nuclear medicine have the expertise to render new biological discoveries into translational tools for quantititively studying biology in humans with nuclear imaging (e.g. PET, SPECT) and treating disease with therapeutic radioisotopes.  In the Evans lab, we aim to breach this gap between chemical biology and nuclear medicine. 

Research in the Evans laboratory is focused on new biomarker discovery and development for nuclear imaging and therapeutic applications, primarily in oncology.  We are a lab of chemical biologists that interact closely with a diverse set of collaborators, including radiochemists, biomedical engineers, radiologists, and medical oncologists, to develop and translate into humans new imaging tools and therapies.  Training opportunities in the lab are by nature interdisciplinary, and we recruit talented young scientists from a wide variety of disciplines to meet the special challenges embedded within the field of biomarker development.  Our lab is located on the 5th floor of Genentech Hall on the Mission Bay campus of UCSF, a vibrant academic community in close proximity to several close collaborators (e.g. Professors Jim Wells, Charly Craik, Adam Renslo).  Please continue to read below for several examples of projects at the interface of chemical biology and nuclear medicine.


January 2019: The article "Imaging PD-L1 expression with immunoPET" was recognized by the American Chemical Society as one of the top five most read articles in Bioconjugate Chemistry."

January 2018: "Imaging PD-L1 expression with immunoPET" is the most downloaded article within the past 30 days on the website for Bioconjugate Chemistry, and the article is featured on the cover of the January 2018 edition of BC (see above).

January 2018: An manuscript in eLife describing our recent collaboration with the Wells lab at USCF is now online (https://elifesciences.org/articles/31098).  This exciting research applied proteomics to define new actionable cell surface drug targets to treat and specifically detect in vivo with PET cancer cells with hyperactive KRAS.  This work has been highlighted by several news outlets: 




December 2017: "Real time transferrin based PET detects MYC positive prostate cancer" was selected by the editors of Molecular Cancer Research as a part of the "Must Read Collection" for 2017.  The article will be featured at the 2018 AACR national meeting.

November 2017:  The Evans lab was awarded a R01 from the National Institute of Mental Health to develop a new fluorine-18 labeled radioligand to measure glucocorticoid receptor expression in CNS disorders.  The three year grant will culminate in a first in human trial at UCSF!

November 2017: The Evans lab was awarded a Research grant from the Tuberous Sclerosis Alliance to apply proteomics to discover new biomarkers to better image and treat clinically problematic tumors arising from the childhood disorder tuberous sclerosis complex.

September 2017: Research from the Evans lab to develop imaging biomarkers for PET to measure MYC signaling non-invasively in human tumors was featured on the Congressionally Directed Medical Research Program website: http://cdmrp.army.mil/pcrp/research_highlights/17evans_highlight

Prostate Cancer PET Biopsies: Painless Precision Medicine

June 2017: Dr. Michael Evans' lab received an American Brain Tumor Association Discovery Award to continue studying 68Ga-citrate PET/MR in patients with high grade glioma.  The aim of this project is to improve the detection of high grade glioma by measuring mTORC1 signaling in the tumor with 68Ga, a Fe(III) biomimetic that targets the transferrin receptor on tumor cells.

April 2017: Congratulations to former undergraduate researcher Sophie Shen (UC Berkeley) for being accepted into a summer research fellowship at FibroGen, Inc., a bay area biotech company.

April 2017: Congratulations to former undergraduate researcher and technician Loc Huynh for his admission into the PhD program in the Department of Chemistry at University of Florida, as well as receiving the Grinter Fellowship to supplement his stipend.

April 2017:  Dr. Michael Evans' lab received an American Cancer Society Research Scholar Award to continue studying 89Zr-labeled transferrin, a radiotracer for PET that measures mTORC1 signaling in tumor cells non-invasively with PET.

January 2017:  Congratulations to Dr. Matthew Parker for receiving a postdoctoral fellowship from the Department of Defense Prostate Cancer Research Program.  His grant is titled "A Novel Prodrug Strategy to Treat Prostate Cancer by Targeting MYC-Driven Nucleotide Biosynthesis".  Dr. Parker is also co-mentored by Professor Davide Ruggero at UCSF.

January 2017:  Research from the Evans lab was recognized as the Featured Translational Article in the current issue of the Journal of Nuclear Medicine.  http://jnm.snmjournals.org/content/58/1/81

December 2016:  Congratulations to Dr. Charles Truillet on accepting a Professorship in the Department of Biomedical Imaging at the French Alternative Energies and Atomic Energy Commission (CEA).

January 2016:  Congratulations to Dr. Charles Truillet for receiving a postdoctoral fellowship from the Department of Defense Prostate Cancer Research Program.  His grant is titled "Development of radiolabeled transferrin constructs to detect and treat castration resistant prostate cancer".  Dr. Truillet is also co-mentored by Dr. Davide Ruggero of UCSF.

Evans lab article recognized as "Editor's Choice" in Molecular Pharmaceutics - American Chemical Society

2015 SNMMI Highlioghts Lecture, Part 1

Non-Invasive Biomarkers For Prostate Cancer

New Imaging Agent Could Improve Prostate Cancer Diagnosis and Treatment

Transferrin PET Project


Post-doctoral Opportunities

January 2018: The Evans lab is currently seeking exceptional candidates for a postdoctoral appointment focusing on applying proteomics to identify new drug targets for solid tumors.  The ideal candidate should have a PhD or equivalent in chemical biology, and a background in proteomics, antibody development and engineering, and the preclinical assessment of experimental therapies.  Experience with bioconjugation chemistry, and radiochemistry is preferred but not required.

Interested candidates should contact Dr. Evans directly and provide a copy of their CV and references at [email protected].

Graduate Students

January 2018: Dr. Evans is a member of the Chemistry and Chemical Biology graduate program and the lab is openly accepting students. Students interested in rotations should contact Dr. Evans directly via email.  https://ccb.ucsf.edu/


Employment Opportunities for staff positions are posted through the UCSF employment websites


Evans Lab Journal of Nuclear Medicine cover

Examples of cover art from Evans lab publications.  A complete list of Evans lab publications can be found at Michael Evans' UCSF profiles page.


Michael J. Evans, PhD, Evans LabMichael J. Evans, PhD, is an Assistant Professor in Residence in the Department of Radiology and Biomedical Imaging at the University of California, San Francisco. He is an experienced chemical biologist with a focus on molecular imaging, organic chemistry, and biomarker discovery through proteomics. Dr. Evans obtained his PhD in Organic Chemistry from The Scripps Research Institute in La Jolla, California under the supervision of Professor Benjamin Cravatt, followed by postdoctoral fellowship in Molecular Imaging at Memorial Sloan Kettering Cancer Center in New York under the supervision of Professors Charles Sawyers and Jason Lewis. He is the co-author of over 40 publications in peer-reviewed journals like Nature Medicine, eLife, Clinical Cancer Research, and PNAS.   Dr. Evans has received several awards, including a 2013 Young Investigator Award from the Prostate Cancer Foundation, a Pathway to Independence award (K99/R00) from the National Cancer Institute, three Idea Development Awards from the Department of Defense, and a Research Scholar Award from the American Cancer Society.  He was also a scientific co-founder of ORIC Pharmaceuticals, Inc., a bay area biotechnology company dedicated to defining new therapies for treatment refractory cancers.  Dr. Evans is a member of the Chemistry and Chemical Biology graduate program, an adjunct member of the Department of Pharmaceutical Chemistry (https://pharmchem.ucsf.edu/), and a full member of the Helen Diller Family Cancer Center.

Junnian Wei, PhD, Evans LabJunnian Wei, PhD, is a Postdoctoral Fellow in the Evans laboratory. He received his BSc, MSc and PhD in Chemistry from Peking University, China under the supervision of Professor Zhenfeng Xi. After a brief postdoctoral fellowship at the University of California, Los Angeles in Professor Paula Diaconescu group, he joined the Evans lab to study proteomics, radiochemistry, and experimental therapeutics. He is an organometallic chemist with additional experience in organic synthesis, polymer chemistry and DFT calculations.   Dr. Wei is the first or co-author on nearly 20 manuscripts in well respected peer reviewed journals like Journal of American Chemical Society and Angewandte Chemie. He was also the recipient of the National Scholarship for Graduate Students in Chemistry from the Ministry of education of China.

Yung-Hua Wang, Evans LabYung-Hua Wang is a Staff Research Associate, and the Evans lab manager.  He received a B.S. in Chemistry from the University of California, Berkeley, and was an undergraduate researcher in the Evans lab for two semesters prior to joining the lab full-time.  Mr. Wang is a co-author on a manuscript in Bioconjugate Chemistry, and works on several small molecule synthesis projects as well as the preclinical assessment of new radiotracers.

Yangjie Huang, PhD, Evans LabYangjie Huang, PhD, is a Postdoctoral Fellow in the Evans laboratory. He received his BSc (2012) in Chemistry from Guangxi University of China, and PhD (2017) in the college of chemistry at the Fuzhou University of China under the supervision of Professor Zhiqiang Weng. He is an experienced organic chemist and good at organic synthesis, organofluorine chemistry and organometallic complex. Dr. Huang is the first or co-author on nearly 15 manuscripts in well respected peer reviewed journals like Angewandte Chemie and Organic Letters. He joins the Evans lab to study radiochemistry and molecular imaging.

Ning Zhao, PhD, Evans labNing Zhao, PhD received his BSc (2010) in Chemistry from Lanzhou University, China and a Ph.D. (2016) in Organic Chemistry from Louisiana State University under the supervision of Professors Dr. Graca Vicente and Dr. Kevin Smith.  Dr. Zhao is an experienced organic chemist with experience in the development of new chemistry for functionalizing fluorescent dyes and carborane clusters for coupling to bioactive molecules.  He is the first or co-author on more than 10 publications in well-respected peer-reviewed journals like the Journal of Organic Chemistry, Bioconjugate Chemistry, and Chemistry – a European Journal. 

Zhuo Chen, Ph.D., Zhuo Chen, PhD is a Postdoctoral Fellow in the Evans lab. She earned her B.S. in Materials Chemistry from Tianjin University, China, and a M.S. in Chemistry (specializing in polymer science) from the University of Massachusetts Lowell, MA. In 2018, she received her Ph.D. in Chemistry under the supervision of Professor Jeremiah Gassensmith at the University of Texas at Dallas, where she focused on functionalizing virus-like particles as a platform for stimuli-responsive drug delivery and fluorescence imaging. She is a co-author on 8 manuscripts in well-respected peer reviewed journals like Small, Bioconjugate Chemistry, and Chemical Communications.  She has extensive experience in nanoparticle-based therapeutics development and formulation, bioconjugation chemistry and organic synthesis.


Ashwin NagarajAshwin Nagaraj was a student in the Masters in Biomedical Imaging Program in the Department of Radiology and Biomedical Imgaing at UCSF.  He received his BS in Molecular and Cell Biology at the University of Connecticut.  His research in the Evans lab interrogated the relationship between mTORC1 signaling and iron metabolism in human disease.  He is currently studying to become a Doctor of Osteopathic Medicine at Kansas City University of Biomedical Sciences.

Mariaelena NaborsMariaelena Nabors was a student researcher in the Summer Research Training Program at UCSF.  Her research in the Evans lab focused on understanding how oncogenic drivers of glioma remodel the surface-ome.  She is currently a fourth year student at Kansas University studying toward a BS in Biochemistry.


Jeffrey HsiaoJeffrey C. Hsiao  was a student in the Masters in Biomedical Imaging (MSBI) program in the Department of Radiology and Biomedical Imaging at UCSF.  He received his BS in Molecular, Cell, Developmental Biology from University of California Los Angeles in 2016.  His prior research in the lab of Professor Aldons Lusis investigated biomarkers in heart failure models using a systems genetics approach. Jeffrey is now attending the Pharmacology PhD program at Weill Cornell Medical College in New York.

Julia Lee, Evans LabJulia Lee was an undergraduate student at UC Berkeley majoring in chemistry with a minor in toxicology. She will be assisting with the molecular characterization of new PET radiotracers for cancer imaging in the Evans Lab.  Julia is now a PharmD student at the UCSF School of Pharmacy.


Anna Pavlova-Moroz, MD, Evans labAnna Pavlova-Moroz, MD is a visiting scholar in the Evans laboratory.  She successfully graduated from I.M. Sechenov First Moscow State Medical University summa cum laude in Internal Medicine, followed by a residency in Hematology-Oncology in the Department of Chemotherapy and Bone Marrow Transplantation in Russian National Research Center for Hematology.  She is currently a PhD student at Skolkovo Institute of Science and Technology (Skoltech) majoring in Biomedical Science, and the author of several scientific papers and abstracts.

Suzanna Tom, Evans Lab

Suzanna Tom is a third year undergraduate majoring in Chemical Biology at UC Berkeley. She will be studying the pharmacology of new radiotracers for prostate cancer imaging.



Charles Truillet, PhD, Evans LabCharles Truillet, PhD was a Postdoctoral Scholar in the Evans laboratory. He was the recipient of a postdoctoral fellowship from the Department of Defense's Prostate Cancer Research Program. His postdoctoral work was focused on identifying and exploiting for diagnostics and therapy new biomarkers regulated by central oncogenes, including the use of transferrin to measure mTORC1 activity, and the first demonstration in humans that PSMA targeted PET can be used to visualize androgen receptor inhibition in prostate cancer metastases.  During his two year appointment as a postdoctoral fellow, he was a co-author on seven articles (three first author) in well respected peer reviewed journals like Journal of Nuclear Medicine, Clinical Cancer Research, and Molecular Pharmaceutics.  He is currently a Professor with tenure in the Department of Biomedical Imaging at the French Alternative Energies and Atomic Energy Commission (CEA).

Christopher Drake, PhD, Evans LabChristopher R. Drake, PhD, was an Associate Specialist in the Evans lab.  During his appointment, Dr. Drake developed a novel, enzyme catalyzed, site specific radiofluorination strategy for small biomolecules.  This work was disclosed in ACS Chemical Biology.  Dr. Drake is currently a senior radiochemist at Sofie Biosciences, Culver City, CA.

Leila Ranis, MS, Evans LabLeila Ranis, MS, was a Junior Specialist in the Evans lab.   Ms. Ranis received a Bachelor of Science in Chemical Biology from the University of California, Berkeley. She earned a Master of Science from the University of Notre Dame under the supervision of Professor Seth Brown. Her master's thesis focused on the synthesis and reactivity studies of group VI metal complexes, and their applications to green chemistry and renewable energy storage. She is the first author of a manuscript in Inorganic Chemistry. She is a currently a medicinal chemist at BioRad Laboratories, Hercules CA.

Khaled Jami, Evans LabKhaled Jami was an undergraduate volunteer and Staff Research Associate in the Evans lab.  He worked on several small molecule synthesis projects while in the lab. He recently earned his B.S. in Chemistry from University of California Berkeley, and is now currently a staff scientist at ThermoFisher, Inc. in the Los Angeles area. He is currently a PhD student in the Chemistry program at University of California Davis.

Matthew Parker, PhD, Evans LabMatthew Parker, PhD was a Postdoctoral Fellow in the Evans lab.  He is the recipient of a 2016 Department of Defense Prostate Cancer Research Program postdoctoral fellowship.  He received his BSc and MSc in Chemistry from Binghamton University (NY), and his PhD in Chemistry from the University of Pittsburgh under the supervision of Professor Christian Schafmeister.  He is an experienced organic and radiochemist, with five manuscripts published in well respected peer reviewed journals like Journal of the America Chemical Society, Journal of Physical Chemistry A, and Clinical Cancer Research. He was also the recipient of the C. Max Hull Award in Organic Chemistry from Binghamton University, the Lois B. Mackey Award from the University of Pittsburgh, and two poster awards from the American Chemical Society.

Loc Huynh, Evans labLoc Huynh was a Staff Research Associate in the Evans lab.  He received a B.S. degree in Chemistry from the University of California, Berkeley. Mr. Huynh is an experience organic chemist with strong skills in the preclinical assessment of novel small molecule and antibody based radiotracers. He is an author of two manuscripts in Clinical Cancer Research and Molecular Pharmaceutics.  He is currently a PhD candidate in the Department of Chemistry at the University of Florida. 

Sophie Shen, Evans lab

Sophie Shen is currently enrolled in the PharmD program at UCSF.  She previously conducted a work study program in the Evans lab focused on the preclinical evaluation of the pharmacology of new radiotracers, and is now preparing for Pharmacy graduate programs.



Nhan Dang, Evans LabNhan Dang is a second year undergraduate student at UC Berkeley majoring in Chemistry.  He joined the Evans in Spring 2017 to study radiotracer development in cancer models. 



Lisa Wu, PhD was an Associate Specialist in the Evans lab.  She is now an Instructor in the Department of Chemistry, San Francisco State University.


The Evans lab graciously accepts financial support from the following sources:

Funding Sources for Evans Lab

Research Directions

Biomarker discovery for cancer imaging and therapeutics

In collaboration with the Wells lab at UCSF (https://wellslab.ucsf.edu/), we are currently applying proteomics to identify new biomarkers on the surface of genetically defined cancer models that are actionable for antibody development.  Our contribution to the first project from this collaboration was to show that a new Fab targeting a cell surface protein upregulated in cancer cells with hyperactive KRAS (G12V) can be used with PET to measure intracellular KRAS activity in mouse models of cancer (https://elifesciences.org/articles/31098).  Moving forward, we are collaborating closely with the Wells lab to develop several new proteomics data sets to identify cell surface proteins uprregulated by other "undruggable" or poorly druggable oncogenic drivers of cancer.  Antibodies against cell surface proteins upregulated by central oncogenes will be converted into tools for nuclear imaging or radioimmunotherapy.

Measuring androgen receptor signaling in human prostate cancer tumors with PET

Although two potent inhibitors of the androgen receptor (Enzalutamide, Abiraterone) were recently shown to improve overall survival in men with castration resistant prostate cancer, responses are only observed in 50% of patients for about a year.  One explanation for these observations is that we may be “under-dosing” the androgen receptor with the current standard of care doses, and incomplete inhibition of the drug target may lead to poor initial responses or encourage adaptive resistance.  Since we currently have no tools to monitor changes in androgen receptor biology post therapy, my collaborators and I developed a panel of imaging biomarkers to measure androgen receptor biology with positron emission tomography.

Because the androgen receptor is a transcription factor, we mined the AR transcriptome to identify "imageable" AR target genes.  We identified numerous cell surface or secreted antigens against which potent and selective antibodies had been raised.  After coupling the antibodies to radionuclides like copper-64 and zirconium-89, we conducted small animal imaging studies to verify whether cell surface changes in antigen expression levels could bve quantifed wi

th PET, and whether the changes correlated with alterations in intracellular AR signaling levels.  In all cases, the ability to measure post therapy (enzalutamide or orchiectomy) changes in AR activity was visually obvious on the PET scans, and because two of the three radiotracers are already in patients with castration resistant prostate cancer, the opportunity to test the impact of drug dose on patient response was imminent.  These data were published in three manuscripts at PNAS, Cancer Discovery, and the Journal of Nuclear Medicine.

The first human trial at UCSF testing the relationship between AR signaling and PSMA expression:

We have since begun the first human trial at UCSF to test whether PSMA expression is increased in prostate cancer lesions after treatment with androgen deprivation therapy (AR inhibition).  In collaboration with Professors Thomas Hope, Rahul Aggarwal, and Eric Small, we have shown that a PSMA targeted PET scan dramatically intensifies four weeks after the initiation of ADT, consistent with the animal data.  A larger clinical trial

 will be requried to assess the breadth of this "PSMA flair" in humans, and we are actively pursuing this.  These data were recenty published in the Journal of Nuclear Medicine.  These results provide the foundation for testing PSMA PET as a pharmacodynamic biomarker for antiandrogens in patients with castration resistant prostate cancer (CRPC).  Moreover, based on our work, several groups are now evaluating the therapeutic efficacy of combined antiandrogen therapy with PSMA-targeted drug conjugates in patients with CRPC.

Measuring MYC signaling in human tumors with PET

MYC is a validated oncogenic driver of many solid tumors and hematologic malignancies.  Developing an imaging biomarker to measure MYC activity is potentially impactful clinically for a number of reasons.  First, despite a deep appreciation of the role of the transcription factor MYC in cancer initiation and progression in preclinical models (because we can study animal tissues invasively), the cancer community understands very little about the role of MYC activity in human disease.  Our limited knowledge of MYC biology in human disease is primarily due to the challenges in acquiring tissue biopsy for research purposes, especially in late stage, metastatic cancer.  Our hypothesis is that a MYC specific PET biomarker will be accepted into widespread clinical use if the radiotracer is easy and cheap to synthesize, straighforward to implement, and does not incovenience the patient.  Second, it is important to develop an imaging biomarker that measures MYC activity as many indirect inhibitors of MYC (i.e. drugs whose primary target is not MYC, but a protein that regulates of MYC activity) are now undergoing their first clinical evaluation in cancer patients.  Two prominent examples are inhibitors of cyclin dependent kinases (CDK4/6) and BET bromodomain containing proteins (BRD4).  A translational assay to measure MYC activity longitudinally would be crucial to better understand these therapies’ ability to inhibit MYC activity in man, particularly in a phase I/II dose escalation study.  Lastly, with the pending development of the first high sensitivity, whole body PET scanner at UC Davis (http://explorer.ucdavis.edu/), the field may be positioned to conduct the first studies examining the utility of low dose PET as a screening tool in high risk populations, akin to the use of low dose CT for lung cancer screening in former heavy smokers. Oncogene specific imaging probes for well established early drivers of cancer would be ideal to apply for screening to capture actively transitioning cells in high risk patients.

Developing transferrin-based PET as a biomarker of MYC activity:

We developed the first quantitative imaging biomarker to measure MYC activity.  Because MYC is a transcription factor, we reasoned that relative changes in the expression level of an "imageable" MYC target gene could be exploited to quantify the degree of intracellular MYC signaling.  Among the target genes most profoundly impacted by MYC activity is the transferrin receptor (TFRC).  TFRC is a direct MYC target gene and expressed predominantly at the surface of cells (rather than stored intracellularly), making it an attractive therapeutic target.  Moreover, the soluble ligand of TFRC, transferrin (Tf), has been used by the nuclear medicine community  for decades to bring radionuclides to tumors, most notably 67Ga-citrate. 

We developed 89Zr-transferrin by conjugating 89Zr to DFO chelators engineered onto lysine side chains in Tf (Holland, J.P. and Evans, M.J., et al. Nature Medicine, 2011).  89Zr-Tf is exceptionally stable in vivo, and the long half life of zirconium-89 allows for imaging several days post injection, which can improve image quality.  Our first efforts to validate 89Zr-Tf as a biomarker of MYC activity showed that the radiotracer specifically accumulated in MYC driven prostate cancer models, and genetic ablation of MYC completely suppressed radiotracer uptake in prostate cancer cells.  Moreover, using a genetically engineered mouse with MYC specific overexpression in the prostate, we were able to show that 89Zr-Tf can image prostate cancer cells with high MYC activity, as well as preneoplastic cells with high MYC activity.  This was significant, as this was the first demonstration that PET could be used to study aberrant oncogene signaling in non-transformed cells.

We have since shown that the anti-MYC effects of indirect MYC inhibitors can be quantified with 89Zr-Tf PET.  For instance, treatment of B cell lymphoma models with BRD4 inhibitors results in a suppression of 89Zr-Tf uptake in tumors that is driven by MYC inhibition (Doran, M.G. et al. Molecular Pharmaceutics, 2016).  In addition, in collaboration with Scott Lowe at MSKCC (https://www.mskcc.org/research-areas/labs/scott-lowe), we showed that the anti-MYC effects of CDK9 inhibitors in hepatocellular carcinoma could be quantified with 89Zr-Tf PET (Huang, C-H. et al. Genes and Development, 2015). Both of these studies underscore the potentialrole of Tf-based PET in interpreting the pharmacology of indirect MYC inhibitors, and this PET strategy may be highly useful to optimize dose in a phase I/II trial, as well as identify those likely to respond to drug earlier.

The clinical translation of 89Zr-Tf:

The Evans and Lewis lab at MSKCC (https://www.mskcc.org/research-areas/labs/jason-lewis) received NCI support for the clinical translation of 89Zr-Tf in 2013 (R01CA176671).  We have currently completed IND enabling studies, and expect to begin first in man studies in cancer patients in 2018.  

Measuring MYC signaling in human tumors with PET by targeting downstream changes in iron metabolism

Because 89Zr-Tf is an experimental radiotracer not yet in humans, we have also opened the first human studies at UCSF to determine if 68Ga-Tf (formed in situ after intravenous administration of 68Ga-citrate) can detect castration resistant prostate cancer metastases (which can be highly MYC driven).  In collaboration with Drs. Spencer Behr, Rahul Aggarwal, and Eric Small at UCSF, the first dose escalation study was conducted to determine the optimal dose of radiotracer and time post injection for imaging, which we determined to be >3.5 mCi and >3 hours post injection (https://link.springer.com/article/10.1007%2Fs11307-016-0966-5).  In the first eight patients studied, the radiotracer detected approximately 75% of lesions that were registered by bone scan and/or CT.  The appearance of true negatives was significant, as it negates the argument that 68Ga-Tf accumulation at early time points post injection is due to non-specific accumulation in regions with unusual vascularity (i.e. the enhanced permeability and retention effect).  Moreover, the degree of uptake is highly consistent with the well accepted position that MYC hyperactivity is prevalent in CRPC, but perhaps not uniformly overexpressed.  Lastly, the heterogeneity of uptake in tumors, even within the same patient, underscores the potential clinical importance of developing oncogene specific tools, as they could reveal a clinically significant layer of biological heterogeneity that cannot be easily accessed using other diagnostic techniques (e.g. biopsy, analysis of circulating tumor cells or biomarkers).

Because many of the patients are also participating in the SU2C/AACR/PCF sponsored West Coast Dream Team, we have collected biopsies for lesions that have been imaged with 68Ga.  Therefore, we can begin to verify the molecular basis of radiotracer uptake using RNA-seq and companion methodologies like array CGH.  This work is ongoing as we continue to accrue patients, but we recently disclosed the first batch of clinical data showing that 68Ga detects MYC overexpressing prostate cancer metastases (http://mcr.aacrjournals.org/content/15/9/1221.long).  This project is currently sponsored by Prostate Cancer Foundation Young Investigator Awards (PIs: Evans, Aggarwal), and a Department of Defense Idea Development Award (PI: Aggarwal).

Development of a biochemically catalyzed site specific radiofluorination strategy for biomolecules

Although fluorine-18 is widely used clinically for the preparation of small molecule radiotracers, the chemistry applied is often too harsh to be used for the preparation of radiofluorinated small biomolecules (e.g. peptides, diabodies, minibodies).  As the community transitions away from imaging with large biomolecules that require several days post injection to visualize cancer lesions, to smaller biomolecules that can empower same day imaging, there is an urgent need to develop better chemistry for appending short half life radionuclides onto small biomolecules. Development of a biochemically catalyzed site specific radiofluorination strategy
In collaboration with Drs. Charles Craik and Henry VanBrocklin, we have developed a new site specific radiofluorination technology that uses the enzyme lipoic acid ligase A to append a fluorine-18 analogue of lipoic acid to an epitope engineered onto the biomolecule of interest (http://pubs.acs.org/doi/10.1021/acschembio.6b00172) .  Proof of concept chemistry using a Fab to urokinase plasminogen activator receptor (uPAR) showed the bioconjugation chemistry was very high yielding (>90%) under mild conditions and in short time periods (<15 min).  The chemistry also scales to produce large enough quantities of radiotracer for injection into small animals for PET.   We are now applying this chemistry to study other antigens of interest to cancer imaging.