Synthesis and Evaluation of [ 123I]-Iodo-PK11195 for Mapping Peripheral-Type Benzodiazepine Receptors (ω 3) in Heart

An iodinated analog of PK11195, 1-(2-chlorophenyl)- N-methyl- N-(1-methylpropyl)isoquinoline-3-carboxamide, a specific antagonist of the peripheral-type benzodiazepine receptor (ω 3), has been synthesized in three steps with an overall chemical yield of 40%. Both [ 123I]- and [ 125I]-Iodo-PK11195 have been synthesized by solid-state isotopic exchange in >60% isolated radiochemical yield and specific activity of 233–348 mCi/mmol. Tissue distribution studies in rats indicate a high uptake of radioactivity in adrenal glands, heart, lung and kidneys, which was blocked 63–87% by preadministration of cold PK11195. Single photon emission computer tomography (SPECT) imaging of the canine heart has been accomplished with [ 123I]PK11195. These results suggest that [ 123I]PK11195 has potential as a SPECT radiotracer for studying the ω 3 receptor in humans.