Reproducibility of binding potential in a single PET scan with multiple injections of [¹¹C]raclopride to evaluate dopamine release

Objectives Regional dopamine release due to neuropsychological tasks can be evaluated by the change in [¹¹C]raclopride binding between the baseline and the stimulated state using PET. Recently, multiple-injection (MI) approach was developed to detect changes in binding potential during a single PET scan using multiple bolus injections of [¹¹C]raclopride. To investigate the feasibility of applying MI approach to measure the change in dopamine release in human, we investigated the reproducibility of binding potential between two rest conditions without tasks, and compared with that by a conventional bolus-plus-continuous infusion (B/I) approach.

Methods PET studies were performed on ten healthy volunteers with the MI and B/I approaches under rest conditions. In the MI studies, [¹¹C]raclopride was administered by a bolus injection at the beginning of the scan (181-232 MBq) and at 45 min after start of scan (148-207 MBq). Binding potentials of two rest condition (BP₁ and BP₂) in the striatum were estimated by a simplified reference tissue model using scan frames from 0 to 40 and 45 to 85 min. The residual radioactivity of the first injection was taken account for BP₂ estimation. In the B/I studies, a bolus injection of [¹¹C]raclopride (232-292 MBq; 50% of the total volume) was followed by a constant infusion. BP₁ and BP₂ were estimated from striatum/cerebellum radioactivity ratio from 40 to 52 and 68 to 100 min of frames, respectively. The reproducibility was evaluated by the mean absolute difference (MAD) between BP₁ and BP₂ and intraclass correlation coefficient (ICC).

Results Both methods showed small MAD (< 5%) between BP₁ and BP₂. The MI approach showed better ICC (0.96) than the B/I approach (0.70). BP values estimated by the MI approach agreed well with those by the B/I approach.

Conclusions The MI approach with [¹¹C]raclopride provides reliable BP estimates with high reproducibility. This approach can be applied to evaluate dopamine release due to neuropsychological tasks.