期刊
NEUROPSYCHOPHARMACOLOGY
卷 34, 期 1, 页码 187-203出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/npp.2008.166
关键词
positron emission tomography; magnetic resorance imaging; occupancy; dose finding; proof-of-concept; proof of mechanism
资金
- NIH [RO1 AA12839]
- NIDA [K24 DA00412-01A1]
- NIMH [9R01MH078175-04A1]
- Lilly Research Labs
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH078175] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM [R01AA012839] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [K24DA000412] Funding Source: NIH RePORTER
Neuroimaging, particularly that of neuroreceptor radioisotope and functional magnetic resonance imaging (fMRI), has played a fundamental role in neuropharmacology and neurophysiology. Because of the unique and pioneering role, especially of the radiolabeling of central nervous system (CNS) drugs for receptor and neurotransmitter system imaging, there is an increasingly major role to aid in CNS drug development. One component is providing evidence for proof of concept of the target for which candidate drugs are being tested for receptor occupancy mechanism of action and ultimately rational drug dosing. There is also a role for other areas of neuroimaging, including fMRI and magnetic resonance spectroscopy in other magnetic resonance-based techniques that, together with radioisotope imaging, represent 'CNS molecular imaging.' The role of these approaches and a review of the recent advances in such neuroimaging for proof-of-concept studies is the subject for this paper. Moreover, hypothetical examples and possible algorithms for early discovery/phase I development using neuroimaging provide specific working approaches. In summary, this article reviews the vital biomarker approach of neuroimaging in proof of concept studies.
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