Radiosynthesis and preliminary evaluation of 5-[I-123/125]iodo3-(2(S)-azetidinylmethoxy)pyridine: A radioligand for nicotinic acetylcholine receptors

The radiochemical syntheses of 5-[I-125]iodo-3-(2 (S)-azetidinylmethoxy)pyr idine (5-[I-125]iodo-A-85380, [I-125]1) and 5-[I-123]-iodo-A-85380, [I-123] 1, were accomplished by radioiodination of 5-trimethylstannyl-3-( (1-tert-b utoxycarbonyl-2 (S)-azetidinyl)methoxy)pyridine, 2, followed by acidic depr otection. Average radiochemical yields of [I-125]1 and [I-123]1 were 40-55% ; and the average specific radioactivities were 1,700 and 7,000 mCi/mu mol, respectively. Binding affinities of [I-125]1 and [I-123]1 in vitro (rat br ain membranes) were each characterized by a K-d value of 11 pM. Preliminary in vivo assay and ex vivo autoradiography of mouse brain indicated that [I -125]1 selectively labels nicotinic acetylcholine receptors (nAChRs) with v ery high affinity and specificity. These studies suggest that [I-123]1 may be useful as a radioligand for single photon emission computed tomography ( SPECT) imaging of nAChRs. NUCL MED BIOL 26;2:175-182, 1999. Published by El sevier Science Inc.