Radiosynthesis and biodistribution of I-123-labeled antagonists of the histamine H-3 receptor as potential SPECT ligands

We have synthesized three I-123-labeled histamine H-3 receptor ligands, i.e ., [I-123]GR 190028, [I-123]FUB 271, and [I-123]iodoproxyfan, in moderate t o good radiochemical yields via a Cu(+-)assisted I-for-I-123 exchange metho d. Biodistribution in the rat of these compounds revealed high hepatic and pulmonary uptake. Brain uptake was moderate, but for [I-123]iodoproxyfan, b rain uptake was high enough for a pilot single photon emission computed tom ography (SPECT) study in the rabbit. However, for this compound, the cerebr al uptake could not be blocked by a pretreatment with [R]-alpha-methylhista mine, a selective, high-affinity histamine H-3 receptor agonist, both in th e SPECT study in the rabbit and in the biodistribution study in the rat. Ap parently, [I-123]iodoproxyfan is binding to a non-H-3 receptor binding site . None of the three investigated compounds is suitable for use as a SPECT l igand for the H-3 receptor in the brain. NUCL MED BIOL 26;6:651-659, 1999. (C) 1999 Elsevier Science Inc. All rights reserved.