Radiosynthesis of (S)-[18F]T1: The first PET radioligand for molecular imaging of α3β4 nicotinic acetylcholine receptors. (June 2017)

• Record Type: Journal Article
• Authors: Sarasamkan, Jiradanai; Fischer, Steffen; Deuther-Conrad, Winnie; Ludwig, Friedrich-Alexander; Scheunemann, Matthias; Arunrungvichian, Kuntarat; Vajragupta, Opa; Brust, Peter
• Is Part Of: Applied radiation and isotopes. Volume 124(2017:Jun.)
• Page Start: 106
• Page End: 113
• Publication Date: 2017-06
• Subjects: α3β4 Nicotinic acetylcholine receptor -- Click reaction -- Drug addiction -- Positron emission tomography -- 18F-Radioligand (S)-[18F]T1 -- Radiofluorination; Radiology -- Periodicals; Radiation -- Industrial applications -- Periodicals; Nuclear chemistry -- Periodicals; Internet resource; Periodical; 660.298
• DOI: 10.1016/j.apradiso.2017.03.015
• Languages: English
• ISSNs: 0969-8043

Abstract

Abstract: Recent pharmacologic data revealed the implication of α3β4 nicotinic acetylcholine receptors (nAChRs) in nicotine and drug addiction. To image α3β4 nAChRs in vivo, we aimed to establish the synthesis of a [ 18 F]-labelled analog of the highly affine and selective α3β4 ligand ( S )-3-(4-(4-fluorophenyl)-1 H -1, 2, 3-triazol-1-yl)quinuclidine (( S )-T1 ). ( S )-[ 18 F]T1 was synthesized from ethynyl-4-[ 18 F]fluorobenzene ([ 18 F]5 ) and ( S )-azidoquinuclidine by click reaction. After a synthesis time of 130 min ( S )-[ 18 F]T1 was obtained with a radiochemical yield (non-decay corrected) of 4.3±1.3%, a radiochemical purity of >99% and a molar activity of >158 GBq/μmol. The brain uptake and the brain-to-blood ratio of ( S )-[ 18 F]T1 in mice at 30 min post injection were 2.02 (SUV) and 6.1, respectively. According to an ex-vivo analysis, the tracer remained intact (>99%) in brain. Only one major radiometabolite was detected in plasma and urine samples. In-vitro autoradiography on pig brain slices revealed binding of ( S )-[ 18 F]T1 to brain regions associated with the expression of α3β4 nAChRs, which could be reduced by the α3β4 nAChR selective drugAT-1001 . These findings make ( S )-[ 18 F]T1 a potential tool for the non-invasive imaging of α3β4 nAChRs in the brain by PET. Highlights: ( S )-[ 18 F]T1 is a promising α3ß4 nAChR ligand for PET imaging. The novel radioligand ( S )-[ 18 F]T1 was synthesized by click reaction. The potential of ( S )-[ 18 F]T1 was shown by in vitro autoradiography and in vivo evaluation in mice.