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PHOTO OF DR. PIKE

Victor W. Pike, PhD, Section Chief
OVERVIEW


1. General Aim

The Molecular Imaging Branch (MIB) was established by NIMH to expand the power of positron emission tomography (PET) as a modality in neuropsychiatric research. The primary role of MIB is to discover, develop, evaluate and ultimately apply much-needed radiotracers for imaging specific targets in human brain. These targets are usually proteins (e.g. neurotransmitter receptors, transporters, enzymes or protein deposits) whose dysfunction or presence is strongly implicated in one or more neuropsychiatric disorders. PET, in conjunction with suitable radiotracers, provides a uniquely sensitive means for following the involvement of imaging targets in the progression of various disorders in living human subjects, and for assessing the efficacy of established or experimental treatments (e.g. new drugs, surgery or transplants). Also PET is applicable to animal models of disease to enhance basic biological understanding. Excitingly, application of PET to the study of real-time changes in brain activity, such as neurotransmitter release, now appears within reach. Key to realizing the greatest benefit from PET is the generation of a diverse complement of selective radiotracers.

It is widely recognized that PET radiotracer availability greatly lags behind the number of potentially interesting targets. This is unsurprising since successful radiotracers must fulfill a wide array of criteria, which in some cases parallel and in others differ from those of effective drugs. Consequently, candidate attrition in PET radiotracer development is rather high, as in drug discovery. In this demanding endeavor it makes great sense to forge collaborations not only with Academia but also with Pharma in order to access extensive medicinal chemistry and pharmacological expertise, especially in areas where new protein targets have become of interest for neuropsychiatric research. Interaction with Pharma is a cornerstone of the MIB radiotracer development program. To this effect, several Cooperative Research and Development Agreements (CRADAs) have been generated with Pharma to bolster our research program in radiotracer discovery and development. Briefly, the mission of PRSS is to provide chemistry expertise in all aspects of PET radiotracer discovery, development and implementation.

2. History

PRSS was established when Dr. Pike’s appointment to the MIB began in February 2001. For an initial period, Dr. Pike was engaged in the de novo design and oversight of the construction of the chemistry suite, including its radiochemistry, synthesis and analysis laboratories and their physical interaction with the pre-existing cyclotron facilities of the adjacent Clinical Center. Dr. Pike also oversaw the procurement of vital instrumentation, staff recruitment and founding of the Section’s research program. The laboratory suite became ready for occupancy in August 2002, so allowing sophisticated equipment (e.g. hot-cells, automated radiosynthesis apparatus, mass spectrometers, NMR spectrometer and HPLCs) to be installed and then commissioned.

3. Resources

PRSS has access to carbon-11 (t1/2 = 20.4 min) and fluorine-18 (t1/2 = 109.7 min) from the three cyclotrons of the Clinical Center and principally uses the modern GE PETrace cyclotron to provide [11C]carbon dioxide and [18F]fluoride ion to any one of its six hot-cells. These hot-cells are mainly equipped with commercially acquired automated radiosynthesis apparatus, including two Synthia devices, two GE MeI systems (MeI Microlab and FXc), a Bioscan loop methylation module and two GE TRACERLab boxes. The Section has extensive HPLC equipment for compound purification, and for radiotracer purification and analysis, including radiometabolite analysis, plus LC-MS, GC-MS and LC-NMR for identification and analysis of compounds, including their metabolites. Four 4-ft wide fume-hoods support synthetic organic chemistry. Microwave systems exist for organic synthesis (CEM Discover and Voyager) and radiochemistry (CEM Discover and Resonance Instrument 521).

4. Functions

PRSS is engaged in and performs the following functions to fufill its primary mission of novel radiotracer development for brain imaging with PET:

PRSS produce a range of ‘literature’ PET radiotracers of interest to the NIMH/MIB molecular imaging program to fulfill its secondary mission.
The following literature radiotracers were produced and made available to NIMH investigators:

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