Gallezot_2014_Synapse_68_556

OBJECTIVE: (18) F-(-)-NCFHEB (also known as (18) F-(-)-Flubatine) is a new radioligand to image alpha4beta2* nicotinic acetylcholine receptors in vivo with positron emission tomography (PET), with faster kinetics than previous radioligands such as (18) F-2-F-A85380. The goal of this study was to assess the sensitivity of (18) F-(-)-NCFHEB-PET to increases in synaptic acetylcholine concentration induced by acetylcholinesterase inhibitors.
METHODS: Two rhesus monkeys were scanned four times each on a Focus 220 scanner: first at baseline, then during two bolus plus infusions of physostigmine (0.06-0.28 mg/kg), and finally following a bolus injection of donepezil (0.25 mg/kg). The arterial input function and the plasma free fraction fP were measured. (18) F-(-)-NCFHEB volume of distribution VT was estimated using the multilinear analysis MA1 and then normalized by plasma free fraction fP .
RESULTS: (18) F-(-)-NCFHEB fP was 0.89 +/- 0.04. At baseline, (18) F-(-)-NCFHEB VT /fP ranged from 7.9 +/- 1.3 mL plasma/cm(3) tissue in the cerebellum to 34.3 +/- 8.4 mL plasma/cm(3) tissue in the thalamus. Physostigmine induced a dose-dependent reduction of (18) F-(-)-NCFHEB VT /fP of 34 +/- 9% in the putamen, 32 +/- 8% in the thalamus, 25 +/- 8% in the cortex, and 23 +/- 10% in the hippocampus. With donepezil, (18) F-(-)-NCFHEB VT /fP was reduced by 24 +/- 2%, 14 + 3% and 14 +/- 5%, 10 +/- 6% in the same regions. CONCLUSION: (18) F-(-)-NCFHEB can be used to detect changes in synaptic acetylcholine concentration and is a promising tracer to study acetylcholine dynamics with shorter scan durations than previous radioligands. Synapse 68:556-564, 2014. (c) 2014 Wiley Periodicals, Inc.