Chemistry, Probes & Molecular Therapy (CPMT)

The Chemistry, Probes and Molecular Therapy (CPMT) research group in the Department of Radiology and Biomedical Imaging at UCSF focuses on the development of new molecular imaging tools. This research group will complement our existing research and infrastructure groups to bring targeted therapies to the clinic, for both for the diagnosis and therapy of human disease.

About Chemistry, Probes & Molecular Therapy (CPMT)

CPMT conference schedule

Meetings related to the activities of the Chemistry, Probes and Molecular Therapy (CPMT) group will be held on Tuesday afternoons, at China Basin Landing in room 342, unless otherwise noted. The goal is 4-5PM with the exception of longer faculty meetings. These include:

  1. CPMT faculty meetings. These are held quarterly and include AIT SRG faculty members.
  2. Clinical research in progress (CRIP). These are designed for clinical researchers to discuss projects.
  3. Nuclear imaging research. Postdoctoral fellows in the Wilson, VanBrocklin, Flavell, and Evans labs will be presenting biweekly (Dr. Dave Korenchan and Barbara Green organizing). Researchers at all levels from Mission Bay groups are invited to join.
  4. Visiting speakers. Invited speakers will present on Tuesday afternoons. We welcome suggestions from all CPMT members.

Barbara Green ([email protected]) will be our contact administrator for the CPMT and related research meetings.

Scheduled meetings (updated weekly):

Aug 20 Dongdong Liang
Sept 24 CPMT faculty meeting
Sept 17 Joe Blecha
Title:  Real Time Arterial Sampling During MicroPET Imaging; Challenges and Findings
Abstract:  MicroPET imaging affords researchers valuable data while interrogating various disease states. Often the quantitative data is derived from the images assuming the tracer is intact over the imaging time period. However, when using metabolically instable PET imaging agents or prodrugs, the imaging findings need to be supported with arterial sampling from the small animal that is being imaged. Processing of the arterial samples is done in a tracer by tracer basis and needs to be thoroughly proven as accurate so that the radioactive species are separable at any given time point. This presentation will highlight a couple of the compounds that have been analyzed in our lab and talk about the challenges of arterial sampling as well as the findings. 
Oct 1 Junnian Wei
Title:  Profiling the surfaceome identifies therapeutic targets for cells with hyperactive mTORC1 signaling.
Abstract:  Aberrantly high mTORC1 signaling is a known driver of many cancers and human disorders, yet pharmacological inhibition of mTORC1 rarely confers durable clinical responses. To explore alternative therapeutic strategies, herein we conducted a proteomics survey to identify cell surface proteins upregulated by mTORC1. A comparison of the surfaceome from Tsc1-/- versus Tsc1+/+ mouse embryonic fibroblasts revealed 59 proteins predicted to be significantly overexpressed in Tsc1-/- cells. Further validation of the data in multiple mouse and human cell lines showed that mTORC1 signaling most dramatically induced the expression of the proteases neprilysin (NEP/CD10) and aminopeptidase N (APN/CD13). Functional studies showed that constitutive mTORC1 signaling sensitized cells to genetic ablation of NEP and APN, as well as the biochemical inhibition of APN.  In summary, these data show that mTORC1 signaling plays a significant role in the constitution of the surfaceome, which in turn may present novel therapeutic strategies.
Oct 8

Clinical Research in Progress (CRIP) group meeting
Presenter:  Dr. Tom Hope, MD will discuss research review

Oct 15 Dongdong Liang
Talk title: Developing positron emission tomography sensors of IDHm for detecting low-grade glioma.
Abstract: Isocitrate dehydrogenase IDH1 and IDH2 are metabolic enzymes that catalyze the conversion of isocitrate to alfa-ketoglutarate (α-KG) in cells. Genes encoding for IDH1 and IDH2 are mutated in >80% of grade II and III gliomas and secondary glioblastomas. Mutant IDH1/2 lose their normal catalytic activity but gain the ability to convert α-KG to 2-hydroxyglutarate (2-HG). 2-HG has a structure similar to α-KG and competitively inhibits several of the α-KG-dependent dioxygenases in cells, thereby, playing a role in tumor initiation. IDH mutations are the earliest genetic changes in the formation of low-grade gliomas. On the other hand, glioma patients with IDH1/2 mutations are found to have significantly longer survival compared to those with normal IDH1 tumors, suggesting the use of these mutations as prognostic biomarkers. IDH mutations are analyzed by ex vivo procedures and currently, there is no clinically applicable method available for noninvasive detection of these mutations in cancers. We aim to develop a positron emission tomography (PET) imaging method using radiolabeled probes to image IDH1 mutations, with the goal of addressing the critical need for an imaging biomarker to study these cancer-associated mutations.
Oct 29 Matt Parker
Talk title: PET imaging of bacterial infection by targeting peptidoglycan.
Abstract: A reliable imaging modality to probe live bacterial infection is still an unmet clinical need as the current methods of detection rely on indirect consequences of infection like morphologic changes or host immune response.  Our central hypothesis is that D-amino acids (DAA) could be used as a specific marker for live bacterial infections in vivo. Most bacteria produce and incorporate DAAs into the peptidoglycan cell wall, most specifically D-alanine. To this end, we have made use of D-[11C]methionine and D-[11C]alanine as PET imaging tracers for bacterial infection.  I will present our most recent findings from imaging studies of these and other supporting tracers in a variety of preclinical models as well as some progress toward next generation tracers.
Oct 31 Dr. Ming-Kai Chen, Yale University
Talk title: PET Imaging of Synaptic Density in Alzheimer's Disease
Nov 12 Jianbo Liu
Location:  Large conference room
Title: Direct Desulfurfluorination of Silver(I) difluoromethanethiolate with 18F− to Label Aryl-OCF3.
Summary: Positron emission tomography (PET) plays key roles in medical imaging, as well as drug discovery and development. However, there is a dearth of efficient and practical radiolabeling methods for 18F-Labeling of Aryl-OCF3, which limits advancements in PET radiotracer development. Here, we design a mild method for the fluorine-18(18F)–desulfurfluorination of Silver(I) difluoromethanethiolate by an [18F]F salt. This strategy may be applied to the synthesis of a wide range of 18F-labeled Aryl-OCF3, including pharmaceutical compounds. The labelling Aryl-OCF3 can be isolated efficiently apart from the pure salt mixture with this strategy, which provides chemists with a new platform to develop the synthesis and discovery of radiotracers and radioligands currently not within research.
Nov 26
Thomas Hayes
Title: Development of 18F and 11C PET Traces for Diagnostic Imaging and Therapy Evaluation.
Location: 4pm in the large conference room
Abstract:  During my time here at UCSF, I have had to work on a large number of projects involving 11C and 18F imaging agents.  These projects have been using a combination of automated, and hand chemistry, especially loop synthesis of labeled molecules for tracer production.  In this meeting I will talk about several of these projects, the capabilities of the ELIXYS system and 11C loop chemistry for the production of labeled tracers, as well as some of the results from those projects.
Dec 10 Ning Zhao
Dec 17

Brian Miller
Title:  Development & Applications of the iQID Camera: A Quantitative, Single-Particle Imaging Detector for small-animal SPECT and Targeted Radionuclide Therapy.
Location:  4pm, Classroom 331

Zoom info: https://ucsf.zoom.us/j/706284991
Meeting ID: 706 284 991
Telephone:  US: +1 669 900 6833 or +1 646 558 8656

 

Jan 21

Ella Jones

Who we serve

The CPMT’s research will translate to healthier futures for:

  • Personalized medicine
  • Individual patient care according to unique metabolic, genetic, and biochemical profiles

Conditions we address

The clinical application of our research includes special focus on:

  • Cancer
  • Infection
  • Neurodegenerative disease

Who we partner with

We look forward to building relationships a wide range of partners:

  • Patients and their families
  • Researchers from our own and other institutions
  • Visionaries who seek to serve the populations we do
  • Donors committed to improving the lives of others

Who we are

The CPMT is made up of:

  • Clinical and research faculty
  • Radiochemists, physicists, spectroscopists, and nuclear medicine physicians
  • Postdoctoral fellows
  • Research staff
  • Medical and graduate students