IODINE-123-BETA-CIT AND IODINE-123-FPCIT SPECT MEASUREMENT OF DOPAMINE TRANSPORTERS IN HEALTHY-SUBJECTS AND PARKINSONS PATIENTS

Iodine-123-beta-carbomethoxy-3 beta-(4-iodophenyltropane) (CIT) has be en used as a probe of dopamine transporters in Parkinson's disease pat ients using SPECT. This tracer has a protracted period of striatal upt ake enabling imaging 14-24 hr postinjection for stable quantitative me asures of dopamine transporters, and it binds with nanomolar affinity to the serotonin transporter. Iodine-123 fluoro-propyl (FP)CIT is an a nalog of [(123)1]-beta-CIT and has been shown to achieve peak tracer u ptake in the brain within hours postinjection and to provide greater s electivity for the dopamine transporter. The purpose of the present st udy was to compare [I-123]-beta-CIT with [I-123]-FPCIT in a within-sub ject design. Methods: Six Parkinson's disease patients and five health y control subjects participated in one [I-123]-beta-CIT and one [I-123 ]-FPCIT SPECT scan separated by 7-21 days. Controls were imaged at 24 hr postinjection 222 MBq (6 mCi) [I-123]-beta-CIT and serially from 1- 6 hr postinjection 333 MBq (9 mCi) [I-123]-FPCIT. Two imaging outcome measures were evaluated: (9) the ratio of specific striatal activity t o nondisplaceable uptake, also designated V-3(''), at each imaging tim e point; and (b) the rate of striatal washout of radiotracer expressed as a percent reduction per hr for [I-123]-FPCIT. In addition, venous plasma was obtained from the five control subjects after the [I-123]-F PCIT injection for analysis of radio-metabolites. Results: Both [I-123 ]-FPCIT and [I-123]-beta-CIT demonstrated decreased striatal uptake in Parkinson's disease patients compared with the controls with a mean o f V-3('')= 3.5 and 6.7 for [I-123]-beta-CIT (Parkinson's disease and c ontrols, respectively) and a mean of V-3('') = 1.34 and 3.70 for [I-12 3]-FPCIT (Parkinson's disease and controls, respectively). For [I-123] -beta-CIT, the mean Parkinson's disease values represented 52% of the control uptake, while the mean [I-123]-FPCIT value for Parkinson's dis ease patients was 37% of the control values. Analysis of [I-123]-FPCIT time-activity curves for specific striatal counts showed washout rate s of 8.2%/hr for Parkinson's disease and 4.9%/hr for controls. Conclus ion: These data suggest that SPECT imaging with [I-123]-FPCIT visually demonstrates reductions in striatal uptake similar to [I-123]-beta-CI T. Iodine-123-FPCIT washed out from striatal tissue 15-20 times faster than [I-123]-beta-CIT, and estimates of dopamine transporter loss in Parkinson's disease patients were higher for [I-123]-FPCIT than for [I -123]-beta-CIT. This was most likely due to the faster rate of striata l washout and establishment of transient equilibrium binding condition s at the dopamine transporter, which the modeling theory suggests prod uces an overestimation of dopamine transporter density with relatively greater overestimates in healthy control subjects by [I-123]-FPCIT.