STRIATAL DOPAMINE TRANSPORTER IMAGING IN NONHUMAN-PRIMATES WITH IODINE-123-IPT SPECT

The regional distribution, kinetics and pharmacological specificity of a new radioiodinated cocaine analog, N-((E)3-iodopropen-2-yl)-2 beta-carbomethoxy-3 beta-(4-chlorophenyl tropane ([I-123]IPT) were examined in brain SPECT studies (n = 20) of nonhuman primates. Methods: Radiolabeling and purification of the iododestannylated trialkyltin precursor yielded the tracer at greater than 90% radiochemical purity and high (>20,000 Ci/mmole) specific activity. Cynomologous monkeys were injected with 7.2 +/- 1.3 mCi (mean +/- s.d.) of the tracer, and serial 10-min images were acquired (total scan time = 177 +/- 22 min). Images were reconstructed as transaxial slices (2 mm) using restorative techniques (Wiener prefiltering). Results: Radioactivity concentrated quickly in striatal regions (time of peak = 25 +/- 13 min) and cleared gradually thereafter(8.8 +/- 4.6 %/hr). Striatal-to-cerebellar ratios of 2.6 +/- 1.5 (n = 19), 6.7 +/- 3.2 (n = 20), 15.1 +/- 10.7 (n = 10) and 22.8 +/- 11.0 (n = 9) were observed at the time of peak and at 1, 2 and 3 hr p.i., respectively. In contrast, extrastriatal activity peaked earlier and at lower levels, cleared more rapidly and resembled cerebellar time-activity curves. Displacing doses of nonspecific antagonists of monoamine transporters (mazindol and beta-CIT) showed that 95% of specific [(131)]IPT binding was reversible, while selective antagonists (e.g., paroxetine, nisoxetine and GBR 12909) demonstrated that striatal activity was specifically associated with dopamine transporters. Conclusion: These results indicate that [123I]lPT is a useful radioligand for in vivo SPECT imaging of striatal dopamine transporters.