ACTIVE AND INACTIVE ENANTIOMERS OF 2-BETA-CARBOMETHOXY-3-BETA-(4-IODOPHENYL)TROPANE - COMPARISON USING HOMOGENATE BINDING AND SINGLE-PHOTONEMISSION COMPUTED TOMOGRAPHIC IMAGING

2 beta-Carbomethoxy-3 beta-(4-iodophenyl)tropane (beta-CIT; also desig nated RTI-55) is an analog of cocaine that has been developed as a sin gle photon emission computed tomography radiotracer that labels dopami ne and serotonin transporters. We have prepared the I-125- and I-123-l abeled ([1R] ''active'' and [1S] ''inactive'') enantiomers of beta-CIT . Total homogenate binding of the I-125-labeled inactive isomer to bab oon caudate and cortex was approximately equal to nonspecific binding of the active isomer in cortex and much lower than total binding of th e active isomer in caudate. However, inactive isomer homogenate bindin g in caudate was somewhat higher than in cortex, and during single pho ton emission computed tomography scanning in vivo striatal (1S)-[I-123 ]beta-CIT uptake was also slightly greater than in cortex. Following i ntravenous administration of the I-123-labeled enantiomers, the plasma clearances of the active and inactive enantiomers were not significan tly different. Single photon emission computed tomography imaging demo nstrated that a bolus dose of nonradioactive (1R)-beta-CIT rapidly dis placed the uptake of (1R)-[I-123]beta-CIT. In contrast, the brain upta ke of (1S)-[I-123]beta-CIT was not displaced by nonradioactive (1R)-be ta-CIT using either a bolus (''kinetic'') or bolus plus constant infus ion (''equilibrium'') paradigm for administration of the radiotracer. In scans with bolus administration of radiotracer, peak striatal uptak e of the active isomer was approximately twice that of the inactive is omer. In comparison to the I-123-labeled active tracer, the inactive t racer showed earlier times to peak activity and faster washouts of act ivity in all brain regions. These studies demonstrate beta-CIT stereos electivity using both homogenate binding and in vivo imaging and sugge st that the inactive enantiomer may be a useful measure of the kinetic s of both blood-brain barrier transport and nonspecific binding.