Victor Pike, Ph.D.
Dr. Pike received his B.Sc. (Hons) degree in chemistry from the University of Birmingham (UK) in 1972 and his Ph.D. in organic chemistry from the same University in 1975. Following a postdoctoral fellowship at Birmingham University, he joined the MRC Cyclotron Unit (Imperial College, London) in 1978 at the foundation of its strong research program in positron emission tomography (PET), eventually becoming Head of its Chemistry and Engineering Section with a strong personal interest in all chemical aspects of the discovery, development and evaluation of novel radioactive probes for molecular imaging with PET. Dr. Pike was awarded the Marie Curie Award and Springer Prize for his work in this area. He joined the Molecular Imaging Branch of NIMH in 2001 as Chief of the PET Radiopharmaceutical Sciences Section (PRSS).
Dr. Pike’s Section is focused on developing novel radioactive probes (radiotracers) for the investigation of neuropsychiatric disorders with PET. This research mainly encompasses medicinal chemistry for probe discovery and radiochemistry for labeling candidate probes with a short–lived positron-emitter, invariably cyclotron-produced carbon-11 (t1/2 = 20 min) or fluorine-18 (t1/2 = 110 min).
PET is a uniquely powerful means for investigating the biochemical workings of the brain in living human subjects, including those suffering from neuropsychiatric disorders. The power of PET in clinical research derives from the use of radiotracers that are specific for a particular important biochemical process (e.g., glucose metabolism) or a low-density protein target (e.g., a neurotransmitter receptor), where the process or target is suspected of playing a major role in one or more brain disorders (e.g. the serotonin transporter in depression). Currently, radiotracers do not exist for the myriad of possible targets. The discovery and development of suitable radiotracers is in fact a major challenge in realizing the full research potential of PET (much like drug discovery).
In Dr. Pike’s laboratory, radiotracers for imaging and quantifying various protein targets (e.g., plaques, transporters, or neurotransmitter receptors) in brain are in development. These targets include Aβ-amyloid plaque, TSPO (previously known as PBR) binding sites, the efflux transporter P-gp and the receptors mGluR5, CB1 and 5-HT1A. Candidate probes are evaluated in animal and normal human subjects in close cooperation with the Imaging Section of the Molecular Imaging Branch, led by Dr. Innis. Successful probes are then introduced into clinical studies with PET for investigating various disorders, such as neuroinflammatory conditions (stroke, Alzheimer’s disease, and traumatic brain injury), addiction (alcoholism), autism, anxiety and depression.
Development of methodology for radiolabeling with carbon-11 and fluorine-18 is key to successful radiotracer development, and is a major component of the Section's research. Currently, this includes the exploration of i) methods to accelerate labeling reactions (e.g., the use of microfluidics or microwaves), ii) chemistry to allow fluorine-18 to be introduced into previously inaccessible molecular positions, iii) semi-robotic approaches to safe and reliable radiotracer production, and iv) the use of mass spectrometry to independently verify radiotracer specific activity, investigate metabolic pathways and provide arterial input functions for PET imaging.
A full list of publications and more information on the research activities of Dr. Pike’s laboratory are available at the laboratory Web Site.
Nucleophile assisting leaving groups: a strategy for aliphatic 18F-fluorination. Lu S, Lepore SD, Li SY, Mondal D, Cohn PC, Bhunia AK, Pike VW. J Org Chem. 2009 Aug 7;74(15):5290-6. doi: 10.1021/jo900700j. PMID: 19572583.
Single-step high-yield radiosynthesis and evaluation of a sensitive 18F-labeled ligand for imaging brain peripheral benzodiazepine receptors with PET. Briard E, Zoghbi SS, Siméon FG, Imaizumi M, Gourley JP, Shetty HU, Lu S, Fujita M, Innis RB, Pike VW. J Med Chem. 2009 Feb 12;52(3):688-99. doi: 10.1021/jm8011855. PMID: 19119848.
Radiodefluorination of 3-fluoro-5-(2-(2-[18F](fluoromethyl)-thiazol-4-yl)ethynyl)benzonitrile ([18F]SP203), a radioligand for imaging brain metabotropic glutamate subtype-5 receptors with positron emission tomography, occurs by glutathionylation in rat brain. Shetty HU, Zoghbi SS, Siméon FG, Liow JS, Brown AK, Kannan P, Innis RB, Pike VW. J Pharmacol Exp Ther. 2008 Dec;327(3):727-35. doi: 10.1124/jpet.108.143347. Epub 2008 Sep 19. PMID: 18806125.
Synthesis and evaluation of [N-methyl-11C]N-desmethyl-loperamide as a new and improved PET radiotracer for imaging P-gp function. Lazarova N, Zoghbi SS, Hong J, Seneca N, Tuan E, Gladding RL, Liow JS, Taku A, Innis RB, Pike VW. J Med Chem. 2008 Oct 9;51(19):6034-43. doi: 10.1021/jm800510m. Epub 2008 Sep 11. PMID: 18783208.
Synthesis and simple 18F-labeling of 3-fluoro-5-(2-(2-(fluoromethyl)thiazol-4-yl)ethynyl)benzonitrile as a high affinity radioligand for imaging monkey brain metabotropic glutamate subtype-5 receptors with positron emission tomography. Siméon FG, Brown AK, Zoghbi SS, Patterson VM, Innis RB, Pike VW. J Med Chem. 2007 Jul 12;50(14):3256-66. Epub 2007 Jun 16. PMID: 17571866.
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