In vitro and ex vivo autoradiographic studies of nicotinic acetylcholine receptors using [18F]fluoronorchloroepibatidine 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 [F-18]exo-2-(2'-fluoro-5'-pyridinyl)-7-azabicylo[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 [[F-18]NFEP to rat thalamic homogenate was consistent with a single class of binding site with a Kd value of 71 FM. 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 [F-18]NFEP as a radioligand for PET studies of nAcChR in the living human brain. NUCL MED BIOL 25;5: 449-454 1998. (C) 1998 Elsevier Science Inc.