Comparison of [123I]ß-CIT and [123I]IPCIT as single-photon emission tomography radiotracers for the dopamine transporter in nonhuman primates

Single-photon emission tomographic (SPET) imaging with the radiotracer [¹²³I]2ß-carbomethoxy-3ß-(4-iodophenyl)tropane ([¹²³I]ß-CIT) has been reported to be a useful in vivo measure of dopamine (DA) transporters. However, in addition to its high DA transporter affinity,ß-CIT also binds with high affinity to serotonin (5-HT) transporters. 2ß-Carboisopropoxy-3ß-(4-iodophenyl)tropane (IPCIT) has been demonstrated by in vitro studies to have higher selectivity for the DA transporter. We compared [¹²³I]ß-CIT and [¹²³I]IPCIT SPET imaging and plasma metabolite analyses in baboons to evaluate the potential advantages of [¹²³I]IPCIT for quantitative in vivo measurements of DA transporter densities. Both tracers had low levels (2% of total plasma¹²³I activity) of lipophilic radiolabeled metabolites at 420 min. [¹²³I]IPCIT had significantly higher binding to plasma proteins. The average percent free (nonprotein bound) [¹²³I]ß-CIT and [¹²³I]IPCIT were 52%±7% and 14%±6%, respectively. Region of interest uptake data were normalized by injected dose and body weight. Consistent with the high density of 5-HT transporters in the midbrain and the lower 5-HT transporter affinity of IPCIT, the normalized peak specific midbrain uptake of [¹²³I]ß-CIT (1.7±0.5) was higher than that of [¹²³I]IPCIT (0.4±0.2). Consistent with its greater lipophilicity, [¹²³I]IPCIT had higher nonspecific uptake, such that normalized cerebellar uptake of [¹²³I]IPCIT was about twice that of [¹²³I]ß-CIT. The ratio of specific to nonspecific uptake in striatum was greater for [¹²³I]ß-CIT compared to [¹²³I]IPCIT; however, striatal binding potentials and distribution volumes were not significantly different. In conclusion, [¹²³I]IPCIT demonstrated in vivo a higher DA transporter selectivity and higher level of nonspecific uptake.