SYNTHESIS AND EVALUATION OF [I-123] IODO-PK11195 FOR MAPPING PERIPHERAL-TYPE BENZODIAZEPINE RECEPTORS (OMEGA(3)) IN HEART

An iodinated analog of PK11195, thyl-N-(1-methylpropyl)isoquinoline-3- carboxamide, a specific antagonist of the peripheral-type benzodiazepi ne receptor (omega(3)), has been synthesized in three steps with an ov erall chemical yield of 40%. Both [I-123]- and [I-125]-Iodo-PK11195 ha ve 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 i n adrenal glands, heart, lung and kidneys, which was blocked 63-87% by preadministration of cold PK11195. Single photon emission computer to mography (SPECT) imaging of the canine heart has been accomplished wit h [I-123]PK11195. These results suggest that [I-123]PK11195 has potent ial as a SPECT radiotracer for studying the omega(3) receptor in human s.