Human Brain Imaging of alpha 7 nAChR with [ super(18)F]ASEM: a New PET Radiotracer for Neuropsychiatry and Determination of Drug Occupancy

Purpose: Using the alpha 7-nAChR radiotracer, [ super(18)F]ASEM, we present the first successful human positron emission tomography (PET) studies. Rodent occupancy with three clinically employed alpha 7-nAChR drugs confirms the specificity of the radiotracer. Procedures: Five healthy male subjects w...

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Bibliographic Details
Published in:Molecular imaging and biology 2014-10, Vol.16 (5), p.730-738
Main Authors: Wong, Dean F, Kuwabara, Hiroto, Pomper, Martin, Holt, Daniel P, Brasic, James R, George, Noble, Frolov, Boris, Willis, William, Gao, Yongjun, Valentine, Heather, Nandi, Ayon, Gapasin, Lorena, Dannals, Robert F, Horti, Andrew G
Format: Article
Language:English
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Papio
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Summary:Purpose: Using the alpha 7-nAChR radiotracer, [ super(18)F]ASEM, we present the first successful human positron emission tomography (PET) studies. Rodent occupancy with three clinically employed alpha 7-nAChR drugs confirms the specificity of the radiotracer. Procedures: Five healthy male subjects were imaged for 90 min following IV [ super(18)F]ASEM. Two subjects were scanned for the second time (test/retest; TRV). Mouse biodistribution of [ super(18)F]ASEM was carried out in CD1 mice injected with using human equivalent doses of DMXB-A, EVP-6124, and varenicline to block specific binding. Results: [ super(18)F]ASEM readily entered the brain and peaked at 15 min post-injection with reversible kinetics and a peak %SUV of about 400 %. The regional human brain distribution of [ super(18)F]ASEM matched previous in vitro data and baboon PET results. The precuneus, parietal, occipital, cingulate cortexes, putamen, and thalamus showed high values of distribution volume (>20 ml/ml) and binding potentials >1 with TRV averaged 10.8 plus or minus 5.1 %. In mouse distribution studies, there was significant dose-dependent blockade in the mouse brain with DMXB-A as well as the other two alpha 7-nAChR drugs. Conclusions: The characteristics of [ super(18)F]ASEM are consistent with the ability to quantify alpha 7-nAChR in the human brain. [ super(18)F]ASEM is suitable for imaging neuropsychiatric disorders and target engagement (receptor occupancy) of potential alpha 7-nAChR drugs.
ISSN:1536-1632
1860-2002
DOI:10.1007/s11307-014-0779-3