Synthesis and evaluation of [I-123]-Iodo-PK11195 for mapping peripheral-type benzodiazepine receptors (omega(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 (omega(3)), has been synthesized in three steps with an overall chemical yield of 40%. Both [I-123]- and [I-125]-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 [I-123]PK11195. These results suggest that [I-123]PK11195 has potential as a SPECT radiotracer for studying the omega(3) receptor in humans.