Premium
Ex vivo and in vivo evaluation of (2 R ,3 R )‐5‐[ 18 F]‐fluoroethoxy‐ and fluoropropoxy‐benzovesamicol, as PET radioligands for the vesicular acetylcholine transporter
Author(s) -
Giboureau Nicolas,
Emond Patrick,
Fulton Roger R.,
Henderson David J.,
Chalon Sylvie,
Garreau Lucette,
Roselt Peter,
Eberl Stefan,
Mavel Sylvie,
Bodard Sylvie,
Fulham Michael J.,
Guilloteau Denis,
Kassiou Michael
Publication year - 2007
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20450
Subject(s) - vesicular acetylcholine transporter , in vivo , ex vivo , chemistry , positron emission tomography , striatum , acetylcholine , nuclear medicine , pharmacology , biochemistry , in vitro , neuroscience , biology , medicine , microbiology and biotechnology , dopamine , choline acetyltransferase
Molecular imaging of the vesicular acetylcholine transporter (VAChT) using positron emission tomography (PET) may provide insights into early diagnosis and better understanding of Alzheimer's disease. We further characterized the VAChT ligand (2 R ,3 R )‐5‐FEOBV ( 1 ) and developed new fluoropropoxy analogues. Ex vivo studies of the new nonradiolabeled analogues (2 R ,3 R )‐5‐FPOBV ( 2 ) ( k D = 0.7 nM) and (2 S ,3 S )‐5‐FPOBV ( 3 ) ( k D = 8.8 nM) were performed in rat brain and showed an enantioselective inhibition of (−)‐5‐[ 125 I]‐IBVM uptake in striatum, cortex, and hippocampus (e.g., 74% for 2 and only 54% for 3 in the cortex). Radiochemical procedures were developed to produce [ 18 F] 1 and [ 18 F] 2 as potential imaging agent for the VAChT. The radiochemistry was carried out in a one step procedure, with radiolabeling yields of 17 and 2.6% (range: 1–5.4), respectively, nondecay corrected with good specific activity: 124–338 GBq/μmol. The radiochemical purity was greater than 98%. The biological (ex vivo and in vivo) properties of these radioligands were evaluated in rats and showed a low (less then 0.1% of the injected dose) and homogeneous brain uptake. The in vivo PET study of [ 18 F] 2 performed in baboon also revealed rapid defluorination as the main problem. Therefore [ 18 F] 1 and [ 18 F] 2 appear to be unsuitable for in vivo imaging of the VAChT using PET. Synapse 61:962–970, 2007. © 2007 Wiley‐Liss, Inc.