In vitro and ex vivo autoradiographic studies of nicotinic acetylcholine receptors using [18F]fluoronochloroepibatidine in rodent and human brain.
A fluorine-18-labeled analog of the potent nicotinic agonist epibatidine is a candidate radioligand for positron emission tomographic (PET) studies of nicotinic acetylcholine receptors (nAcChR). Following intravenous administration of [18F]exo-2-(2'-fluoro-5'-pyridinyl)-7-azabicyclo[2.2.1]heptane (NFEP), high uptake in thalamus was visualized in sections of mouse and rat brain by autoradiography using a phosphor imaging device. Binding of [18F]NFEP to rat thalamic homogenate was consistent with a single class of binding site with a Kd value of 71 pM. In vitro autoradiography of thaw-mounted sections of human thalamus revealed a heterogeneous pattern of binding; Bmax values for ventrolateral nucleus, insular cortex and dorsomedial nucleus, and internal capsule were 20, 8, and 3 pmol/cc of tissue, respectively. However, similar Kd values close to 50 pM were calculated for all regions. These studies support the suitability of [18F]NFEP as a radioligand for PET studies of nAcChR in the living human brain.
Gatley
S J
SJ
Medical Department, Brookhaven National Laboratory, Upton, NY 11973, USA. gatley@bnl.gov
Ding
Y S
YS
Brady
D
D
Gifford
A N
AN
Dewey
S L
SL
Carroll
F I
FI
Fowler
J S
JS
Volkow
N D
ND
D000818:Animals; D001345:Autoradiography; D001549:Benzamides / Q000493:pharmacokinetics; D001921:Brain / Q000000981:diagnostic imaging*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013788:Thalamus / Q000000981:diagnostic imaging / Q000378:metabolism
D001549:Benzamides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D019275:Radiopharmaceuticals; D011978:Receptors, Nicotinic; C115362:fluoronorchloroepibatidine