Phase I clinical study with different doses of Tc-TRODAT-1 in healthy adults.

OBJECTIVES

To study the pharmacokinetics, biodistribution, and injection doses of Tc-TRODAT-1 in healthy adults.

METHODS

Thirty healthy individuals comprising 15 females and 15 males were randomly divided into three groups and the injection doses of Tc-TRODAT-1 of group 1, 2, and 3 were 370 MBq, 740 MBq, and 1110 MBq, respectively. Assessments of subjective symptoms and tests were performed before and after injection. Blood and urine collections and whole-body planar imaging were analyzed at various time points. Bilateral brain striatal SPECT images obtained at 3.5 h PI were assessed visually and semiquantitatively.

RESULTS

No serious adverse events or deaths were observed in our study. The pharmacokinetic analysis showed that Tc-TRODAT-1 was eliminated rapidly from the circulation, with just about 4% of the injected dose remaining in blood at 1 h post-injection. The mean cumulative urinary excretion over 24 h was just 2.96 ± 0.96%ID. The time-activity curve demonstrated that the radioactivity was mainly in liver and abdomen. The highest absorbed dose was in the dose-limiting organ, liver (20.88 ± 4.45 × 10 mSv/MBq). The average effective dose was 5.22 ± 1.05 × 10 mSv/MBq. The clarity of striatal images assessed visually in group 1 was worse than that in group 2 and 3. The semiquantitative analysis showed that there were no differences in striatum/cerebellum between the three groups (group 1: 1.77 ± 0.11, group 2: 1.62 ± 0.14, and group 3: 1.75 ± 0.20; P = 0.088).

CONCLUSIONS

Tc-TRODAT-1 was safe to use in humans and showed the status of dopaminergic neurons specifically and clearly. The injection dose we suggested was 740 MBq.