Iodine-123-IPT SPECT imaging of CNS dopamine transporters: nonlinear effects of normal aging on striatal uptake values

Abstract

Iodine-123-labeled IPT (N-(3-iodopropen-2-yl)-2 beta-carbomethoxy-3 beta-(4-chlorophenyl)tropane) is an analog of cocaine that selectively binds the presynaptic dopamine transporter. This study sought to characterize changes in the striatal uptake of IPT with normal aging.

Methods: The sample included 18 healthy human volunteers. Their ages ranged from 19 to 67 yr. Dynamic SPECT scans of the brain were acquired with about 185 MBq (5 mCi) of IPT on a triple-headed camera. The images were reconstructed with a three-dimensional restorative filter and corrected for attenuation. The mean concentration of radioactivity [microCi/ml] was measured in the head of the caudate and body of the putamen. The remainder of the supratentorial brain was used as a reference.

Results: The specific uptake of IPT was higher in the caudate than in the putamen of each subject. It decreased significantly with age in both regions. The mean specific uptake in seven volunteers who were less than 30 yr old was 17.6 +/- 4.9 in the caudate and 13.3 +/- 4.0 in the putamen, compared to only 11.97 +/- 3.30 and 7.8 +/- 2.68, respectively, in the six middle-aged subjects (t = 2.53 and 2.90, df = 11, p = 0.027 and 0.014). However, there were no significant differences between the six middle-aged subjects and the five volunteers who were older than 60 yr, whose respective means were 9.0 +/- 1.6 and 6.2 +/- 0.7 (t = 1.83 and 1.28, df = 9, p = 0.10 and 0.23). The results were supported by regression analysis, which indicated that changes with age were not optimally described as a linear function when compared to several nonlinear alternatives. The fit improved when the models accounted for relatively rapid rates of decline during young adulthood, followed by less rapid decline throughout middle age.

Conclusion: The results are consistent with the findings from previous studies that have shown that the specific uptake values for radiopharmaceuticals that bind the dopamine transporter decline with advancing age. However, results of this study suggest that the effects of aging may be nonlinear and regionally distinct.