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

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

Research output: Contribution to journalArticle

Abstract

Procedures: Five healthy male subjects were imaged for 90 min following IV [18F]ASEM. Two subjects were scanned for the second time (test/retest; TRV). Mouse biodistribution of [18F]ASEM was carried out in CD1 mice injected with using human equivalent doses of DMXB-A, EVP-6124, and varenicline to block specific binding.

Purpose: Using the α7-nAChR radiotracer, [18F]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.

Results: [18F]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 [18F]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 [18F]ASEM are consistent with the ability to quantify α7-nAChR in the human brain. [18F]ASEM is suitable for imaging neuropsychiatric disorders and target engagement (receptor occupancy) of potential α7-nAChR drugs.

Original languageEnglish (US)
Pages (from-to)730-738
Number of pages9
JournalMolecular Imaging and Biology
Volume16
Issue number5
DOIs
StatePublished - Jan 1 2014

Keywords

  • Alpha-7
  • DMXB-A
  • GTS-21
  • Nicotinic acetylcholine receptor
  • PET brain imaging
  • Radiotracer kinetic modeling
  • Receptor occupancy
  • Schizophrenia

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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