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Imaging and Quantitation of Dopamine Transporters with Iodine-123-IPT in Normal and Parkinson's Disease Subjects

Departments of Nuclear Medicine and Neurology, Asan Medical Center, University of Ulsan, Seoul, Korea

Correspondence: For correspondence or reprints contact: Hee-Joung Kim, PhD, Department of Diagnostic Radiology, Yonsei University, Medical College, 134 Shinchon-dong, Seo-daemoon-Ku, Seoul, Korea, 120-762.

ABSTRACT

Iodine-123-N-(3-iodopropene-2-yl)-2ß-carbomethoxy-32ß-(4-chloropheny) tropane (¹²³I-IPT) is a new dopamine transporter ligand that selectively binds the dopamine reuptake sites. Transporter concentrations have been known to decrease in Parkinson's disease patients. The purpose of this study was to evaluate the usefulness of IPT as an imaging agent for measuring changes in transporter concentrations in Parkinson's disease. Methods: IPT labeled with 6.78 ± 0.67 mCi ¹²³I was injected intravenously asa bolus into eight normal controls (mean age 41 ± 12 yr) and 17 Parkinson's disease patients (mean age 55 2± 9 yr). Dynamic SPECT scans of the brain were then performed for 5 min each over 120 min on a triple-headed gamma camera equipped with medium-energy collimators. Regions of interest were draw non the middle set of the image at the level of the basal ganglia (BG) for each subject. Time-activity curves were generated for the left BG, right BG and occipital cortex (0CC). The empirical ratios between BG - OCC and OCC, which represent specific-to-nonspecific binding ratios, were computed at various time points. The statistical parameter k₃/k₄ was estimated by two methods: a variation of the graphic method that derives the ratio of ligand distribution volumes (R_V), and the area ratio method (R_A), in which the ratio is calculated from the areas under the specific and nonspecfic binding activity curves. Results: The mean (BG - OCC)/OCC ratio for normal controls (3.07 ± 0.73) was significantly higher than that for Parkinson's disease patients at 115 min (1.10 ± 0.56)(p = 2.76 x 1O^–5). The mean R_V and R_A for normal controls were 2.06 ± 0.27 and 1.50 ± 0.15, respectively. The mean R_V, and R_A for Parkinson's disease patients were 0.78 ± 0.31 and 0.65 ± 0.24, respectively. Both R_V and R_A for normal controls were significantly higher than those for Parkinson's disease patients (p values for R_V and R_A were 1.91 x 1O^–8 and 3.46 x 10^–10, respectively). The R_V has linear relationships with both R_A and(BG - OCC)/OCC ratio at 115 min. The R_V has a higher correlation (r = 0.99) with R_A than it does with (BG - OCC)/OCC(r = 0.93). Conclusion: The R_V, R_A and (BG - OCC)/OCC for Parkinson's disease patients were clearly separated from those of normal controls, and they may be useful outcome measures for clinical diagnosis. The simplest (BG - OCC)/OCC ratio, requiring a single late time point, could be useful in clinical situations, whereas R_V or R_A is preferred when the dynamic data are available. The findings suggest that ¹²³I-IPTis a useful tracer for diagnosing Parkinson's disease and studying dopamine reuptake sites.

Key Words: dopamine transporter • SPECT • Parkinson's disease

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