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 (t_1/2 = 20 min) or fluorine-18 (t_1/2 = 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-HT_1A.  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.

• Lu SY, Salvatore SD, Li SY, Modal D, Cohn PC, Bhunia AK, Pike VW: Nucleophile Assisting Leaving Groups: A new strategy for aliphatic ¹⁸F-fluorination, J. Org. Chem., 74: 5290-5296, 2009. (View PDF)
• Briard E, Zoghbi SS, Siméon FG, Imaizumi M, Gourley JP, Shetty HU, Lu SY, Fujita M, Innis RB, Pike VW: Single-step high-yield radiosynthesis and evaluation of a sensitive ¹⁸F-labeled ligand for imaging brain peripheral benzodiazepine receptors with PET, J. Med. Chem., 52: 688-699, 2009. (View PDF)
• Shetty HU, Zoghbi SS, Siméon FG, Liow J-S, Brown AK, Kannan P, Innis RB, Pike VW: 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, J. Pharm. Exp. Ther., 327: 727-735, 2008. (View PDF)
• Lazarova N, Zoghbi SS, Hong J, Seneca N, Tuan E; Gladding RL, Liow J-S, Taku A, Innis RB, Pike VW: Synthesis and evaluation of [N-methyl-₁₁C]N-desmethyl-loperamide as a new and improved PET radiotracer for imaging P-gp function. J. Med. Chem., 51: 6034-6043, 2008. (View PDF)
• Siméon FG, Brown AK, Zoghbi SS, Patterson VM, Innis RB, Pike VW: 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. J. Med. Chem., 50: 3256-3266, 2007. (View PDF)
• Lu SY, Watts P, Chin FT, Hong J, Musachio JL, Briard E, Pike VW: Syntheses of ¹¹C- and ¹⁸F-labeled carboxylic esters within a hydrodynamically-driven micro-reactor. Lab Chip, 4: 523-525, 2004. (View PDF)