A facile, no carrier added method for the preparation of [18F] Drugs and Building Blocks for PET Imaging Princeton docket, # 14-3015

Web Published:
6/30/2014
Description:

A facile, no carrier added method for the preparation of [18F] Drugs and Building Blocks for PET Imaging

 Princeton docket, # 14-3015

Princeton researchers in the department of chemistry together with colleagues at the Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School have developed the first late-stage 18F labeling chemistry for aliphatic C-H bonds with no-carrier-added [18F]fluoride. The method uses Mn-salens or Mn-porphyrins as F-transfer catalysts and enables the facile labeling of a variety of bioactive molecules and building blocks with radiochemical yields (RCY) ranging from 20% to 72% within 10 minutes without the need for pre-activation of the labeling precursor.

The catalyst itself can directly elute [18F]fluoride from an ion exchange cartridge with over 90% efficiency. Using this feature, the conventional and laborious dry-down step prior to reaction is circumvented, greatly simplifying the mechanics of this protocol and shortening the time for automated synthesis.

Proof of concept has been demonstrated in  producing fluorinated derivatives of rasagaline, nabumetone, celestolide, a celecoxib analog, papaverine, a protected enalaprilat, fingolimod, a protected dopamine and ibuprofen.

 

Applications:   

·         [18F]  substitution at C-H  bonds common to  drug and drug like molecules

·         Use with range of functional groups

·         Adaptable to any lab with basic PET chemistry infrastructure

 

Advantages: 

·         No need for target pre-activation

·         Reaction is operationally simple, no dry down and is air and moisture tolerant

·          Enables high throughput radiolabeling of parent compounds and building blocks

·         Increased efficiency of PET tracer synthesis and evaluation.

 

Publications

Late stage benzylic C-H fluorination with  [18F] Fluoride for PET Imaging, Huang X, Liu W, Neelamegam R, Hooker JM, Groves JT, JACS, 2014, 136, 6842-6845

Wei Liu and John T. Groves Mn-Catalyzed Oxidative Benzylic C-H Fluorination Using Fluoride Ion, Angew. Chem. Int. Ed. 2013, 52, 6024-6027.

Liu,W., Huang, X., Cheng, MJ., Nielsen, RJ., Goddard III, W., Groves, JT., Oxidative Aliphatic C-H Fluorination with Fluoride Ion Catalyzed by a Manganese Porphyrin, Science 14 September 2012: 1322-1325

Chemists Score Alkyl Fluorination, Organic Synthesis: Single direct fluorination of C-H bonds adds to research hot streak, p.7, News of the Week, Chemical and Engineering News, Sept. 17, 2012

Principal Investigator and Inventor

Professor John T Groves, Professor of Chemistry

Professor Groves major thrust of research is at the interface of organic, inorganic, and biological chemistry. Many biochemical transformations as well as important synthetic and industrial processes are catalyzed by metals. Current efforts focus on the design of new, biomimetic catalysts and the molecular mechanisms of these processes, the design and assembly of large scale membrane-protein-small molecule constructs, studies of host-pathogen interactions related to iron acquisition by small molecule siderophores and molecular probes of the role of peroxynitrite in biological systems. Professor Groves is a member of the National Academy of Sciences and the recipient of many accolades, including recent awards of the 2010 Hans Fischer Career Award in Prophyrin Chemistry and the 2010 Remsen Award. He also was one of two people selected to receive the 2008 Grand Prix de la Fondation de la Maison de la Chimie, for his work with cytochrome P450 enzymes and model metalloporphyrin catalysts.

Intellectual Property

Patent applications are pending. Princeton is seeking industrial collaborators for the further development and commercialization of this technology

Contact

Laurie Tzodikov
Princeton University Office of Technology Licensing • (609) 258-7256• tzodikov@princeton.edu

 

Patent Information:
For Information, Contact:
Laurie Tzodikov
Licensing Associates
Princeton University
tzodikov@Princeton.EDU
Inventors:
John (Jay) Groves
Xiongyi Huang
Wei Liu
Jacob Hooker
Keywords: