Human Brain Imaging of α7 nAChR with [18F]ASEM: a New PET Radiotracer for Neuropsychiatry and Determination of Drug Occupancy View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-10

AUTHORS

Dean F. Wong, Hiroto Kuwabara, Martin Pomper, Daniel P. Holt, James R. Brasic, Noble George, Boris Frolov, William Willis, Yongjun Gao, Heather Valentine, Ayon Nandi, Lorena Gapasin, Robert F. Dannals, Andrew G. Horti

ABSTRACT

PURPOSE: Using the α7-nAChR radiotracer, [(18)F]ASEM, we present the first successful human positron emission tomography (PET) studies. Rodent occupancy with three clinically employed α7-nAChR drugs confirms the specificity of the radiotracer. PROCEDURES: Five healthy male subjects were imaged for 90 min following IV [(18)F]ASEM. Two subjects were scanned for the second time (test/retest; TRV). Mouse biodistribution of [(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: [(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 [(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 ± 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 α7-nAChR drugs. CONCLUSIONS: The characteristics of [(18)F]ASEM are consistent with the ability to quantify α7-nAChR in the human brain. [(18)F]ASEM is suitable for imaging neuropsychiatric disorders and target engagement (receptor occupancy) of potential α7-nAChR drugs. More... »

PAGES

730-738

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s11307-014-0779-3

DOI

http://dx.doi.org/10.1007/s11307-014-0779-3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1039883959

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25145965


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