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Iodine-123-ß-CIT and Iodine-123-FPCIT SPECT Measurement of Dopamine Transporters in Healthy Subjects and Parkinson's Patients

Departments of Diagnostic Radiology, Neurology and Psychiatry, Yale University School of Medicine, New Haven
Department of Veterans Affairs Medical Center, West Haven, Connecticut

Correspondence: For correspondence or reprints contact: John P. Seibyl, MD, Section of Nuclear Medicine, TE-2 Department of Diagnostic Radiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510.

ABSTRACT

Iodine-123-ß-carbomethoxy-3 ß-(4-iodophenyltropane)(CIT) has been used as a probe of dopamine transporters in Parkinson's disease patients using SPECT. This tracer has a protracted period of striatal uptake enabling imaging 14–24hr postinjection for stable quantitative measures of dopamine transporters, and it binds with nanomolar affinity to the serotonin transporter. Iodine-123 fluoropropyl (FP)CIT is an analog of [¹²³I]-ß-CIT and has been shown to achieve peak tracer uptake in the brain within hours postinjection and to provide greater selectivity for the dopamine transporter. The purpose of the present study was to compare [¹²³I]-ß-CIT with [¹²³I]-FPCIT in a within-subject design. Methods: Six Parkinson's disease patients and five healthy control subjects participated in one [¹²³I]-ß-CIT and one [¹²³I]-FPCIT SPECT scan separated by 7–21 days. Controls were imaged at 24 hr postinjection 222 MBq (6 mCi) [¹²³I]-ß-CIT and serially from 1-6 hr postinjection 333 MBq (9 mCi) [¹²³I]-FPCIT. Two imaging outcome measures were evaluated: (a) the ratio of specific striatal activity to nondisplaceable uptake, also designated V"₃, at each imaging time point; and (b)the rate of striatal washout of radiotracer expressed as a percent reduction per hr for [¹²³I]-FPCIT. In addition, venous plasma was obtained from the five control subjects after the [¹²³I]-FPCIT injection for analysis of radio metabolites. Results: Both [¹²³I]-FPCIT and [¹²³I]-ß-CIT demonstrated decreased striatal uptake in Parkinson's disease patients compared with the controls with a mean of V"₃=3.5 and 6.7 for [¹²³I]-ß-CIT(Parkinson's disease and controls, respectively) and a mean of V"₃ = 1.34 and 3.70 for [¹²³I]-FPCIT(Parkinson's disease and controls, respectively). For [¹²³I]-ß-CIT, the mean Parkinson's disease values represented 52% of the control uptake, while the mean [¹²³I]-FPCIT value for Parkinson's disease patients was 37% of the control values. Analysis of [¹²³I]-FPCIT time-activity curves for specific striatal counts showed washout rates of 8.2%/hr for Parkinson's disease and 4.9%/hr for controls. Conclusion: These data suggest that SPECT imaging with [¹²³I]-FPCIT visually demonstrates reductions in striatal uptake similar to [¹²³I]-ß-CIT. Iodine-123-FPCIT washed out from striatal tissue 15-20 times faster than [¹²³I]-ß-CIT, and estimates of dopamine transporter loss in Parkinson's disease patients were higher for [¹²³I]-FPCIT than for [¹²³I]-ß-CIT. This was most likely due to the faster rate of striatal washout and establishment of transient equilibrium binding conditions at the dopamine transporter, which the modeling theory suggests produces an overestimation of dopamine transporter density with relatively greater overestimates in healthy control subjects by [¹²³I]-FPCIT.

Key Words: dopamine • SPECT • iodine-123-ß-carbomethoxy-3 ß-(4-iodophenyltropane) • dopamine transporter • Parkinson's disease • iodine-123-FP-carbomethoxy-3 ß-(4-iodophenyltropane)

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