Evaluation of the sensitivity of the novel α4β2* nicotinic acetylcholine receptor PET radioligand 18F‐(‐)‐NCFHEB to increases in synaptic acetylcholine levels in rhesus monkeys. Issue 11 (28th July 2014)

• Record Type: Journal Article
• Authors: Gallezot, Jean‐Dominique; Esterlis, Irina; Bois, Frederic; Zheng, Ming‐Qiang; Lin, Shu‐Fei; Kloczynski, Tracy; Krystal, John H.; Huang, Yiyun; Sabri, Osama; Carson, Richard E.; Cosgrove, Kelly P.
• Is Part Of: Synapse. Volume 68:Issue 11(2014)
• Page Start: 556
• Page End: 564
• Publication Date: 2014-07-28
• Subjects: Synapses -- Periodicals; 612
• DOI: 10.1002/syn.21767
• Languages: English
• ISSNs: 0887-4476

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <sec id="syn21767-sec-0001" sec-type="section"> <title>Objective</title> <p> <sup>18</sup>F‐(‐)‐NCFHEB (also known as <sup>18</sup>F‐(‐)‐Flubatine) is a new radioligand to image α4β2* nicotinic acetylcholine receptors in vivo with positron emission tomography (PET), with faster kinetics than previous radioligands such as <sup>18</sup>F‐2‐F‐A85380. The goal of this study was to assess the sensitivity of <sup>18</sup>F‐(‐)‐NCFHEB‐PET to increases in synaptic acetylcholine concentration induced by acetylcholinesterase inhibitors.</p> </sec> <sec id="syn21767-sec-0002" sec-type="section"> <title>Methods</title> <p>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 <italic>f</italic><sub>P</sub> were measured. <sup>18</sup>F‐(‐)‐NCFHEB volume of distribution <italic>V</italic><sub>T</sub> was estimated using the multilinear analysis MA1 and then normalized by plasma free fraction <italic>f</italic><sub>P</sub>.</p> </sec> <sec id="syn21767-sec-0003" sec-type="section"> <title>Results</title> <p> <sup>18</sup>F‐(‐)‐NCFHEB <italic>f</italic><sub>P</sub> was 0.89 ± 0.04. At baseline, <sup>18</sup>F‐(‐)‐NCFHEB <italic>V</italic><sub>T</sub>/<italic>f</italic><sub>P</sub> ranged from 7.9 ± 1.3 mL plasma/cm<sup>3</sup> tissue in the cerebellum to 34.3 ± 8.4 mL plasma/cm<sup>3</sup> tissue in the thalamus. Physostigmine induced a dose‐dependent reduction of <sup>18</sup>F‐(‐)‐NCFHEB <italic>V</italic><sub>T</sub>/<italic>f</italic><sub>P</sub> of 34 ± 9% in the putamen, 32 ± 8% in the thalamus, 25 ± 8% in the cortex, and 23 ± 10% in the hippocampus. With donepezil, <sup>18</sup>F‐(‐)‐NCFHEB <italic>V</italic><sub>T</sub>/<italic>f</italic><sub>P</sub> was reduced by 24 ± 2%, 14 + 3% and 14 ± 5%, 10 ± 6% in the same regions.</p> </sec> <sec id="syn21767-sec-0004" sec-type="section"> <title>Conclusion</title> <p> <sup>18</sup>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. <bold>Synapse 68:556–564, 2014</bold>. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>