title: Localization of IBF as a D-2 dopamine receptor imaging agent in nonhuman primates.
abstract: Preliminary study of iodine-123 labeled IBF, (S)-5-iodo-7-N-[(1-ethyl-2-pyrrolidinyl)methyl] carboxamido-2, 3-dihydrobenzofuran, has demonstrated the potential of using this agent to evaluate the status of the CNS D-2 dopamine receptor in humans. To further characterize this ligand and evaluate single-photon emission tomography (SPET) quantitation, a detailed biodistribution study in monkeys (Macaca fascicularis) with 123I- and 125I-IBF was performed. The dual tracer was simultaneously injected for in vivo imaging, bio-distribution, and ex vivo autoradiography in the same monkey. After the injection, SPET data (10 min/frame x 15) were collected with a triple-head gamma camera. Dynamic imaging data indicated that IBF localized in basal ganglia (BG) with a half life of 90-120 min. Other regions, i.e., cerebellum (CB) and cortex (CX), showed very low uptake. At 2.2 h after the injection, the monkey was sacrificed. Organ distribution data indicated that, as expected, there was a significant uptake in basal ganglia (0.029% ID/g), and the BG/CB and BG/CX ratios were 17.8 and 14.2 respectively. Lower ratios were obtained from SPET image analysis (BG/CB = 3.5 at 2.5 h). The eye uptake was observed with SPET, but was only quantified on autoradiograms with significant uptake (0.017% ID/g). Autoradiography of the eye demonstrated that predominant uptake was localized in the ciliary body and the choroid. The selective retention and high BG/CB ratio of 123I-IBF make it a useful agent for in vivo D-2 dopamine receptor imaging with SPET.
authors.affiliation: Department of Radiology, University of Pennsylvania, Philadelphia 19104.
authors.forename: J J
authors.initials: JJ
authors.lastname: Billings
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Guo
authors.forename: M P
authors.initials: MP
authors.lastname: Kung
authors.forename: H F
authors.initials: HF
authors.lastname: Kung
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000097:blood / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism*; D007457:Iodine Radioisotopes; D008252:Macaca fascicularis; D008297:Male; D011759:Pyrrolidines / Q000097:blood / Q000493:pharmacokinetics*; D017448:Receptors, Dopamine D2; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D001572:Benzofurans; D007457:Iodine Radioisotopes; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; C062439:5-iodo-N-((1-ethyl-2-pyrrolidinyl)methyl)-2,3-dihydrobenzofurancarboxamide