Human brain imaging of α7 nAChR with [(18)F]ASEM: a new PET radiotracer for neuropsychiatry and determination of drug occupancy

Mol Imaging Biol. 2014 Oct;16(5):730-8. doi: 10.1007/s11307-014-0779-3.


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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Animals
  • Azabicyclo Compounds* / blood
  • Azabicyclo Compounds* / chemistry
  • Benzylidene Compounds
  • Brain / diagnostic imaging*
  • Cyclic S-Oxides* / blood
  • Cyclic S-Oxides* / chemistry
  • Humans
  • Male
  • Mice
  • Middle Aged
  • Neuropsychiatry
  • Positron-Emission Tomography*
  • Pyridines
  • Radiopharmaceuticals*
  • Time Factors
  • Tissue Distribution
  • alpha7 Nicotinic Acetylcholine Receptor / metabolism*


  • 3-(1,4-diazabicyclo(3.2.2)nonan-4-yl)-6-fluorodibenzo(b,d)thiophene 5,5-dioxide
  • Azabicyclo Compounds
  • Benzylidene Compounds
  • Cyclic S-Oxides
  • Pyridines
  • Radiopharmaceuticals
  • alpha7 Nicotinic Acetylcholine Receptor
  • 3-(2,4-dimethoxybenzylidene)anabaseine