Initial Evaluation of 11C-DPA-713, a Novel TSPO PET Ligand, in Humans

Translocator protein (TSPO) is upregulated in activated microglia and thus can serve as a marker of neuroinflammation. Recently, a novel radioligand, C-11-N, N-diethyl-2-[2-(4-methoxyphenyl)-5,7dimethyl-pyrazolo[1,5-a]pyrimidin-3-yl]-acetamide (C-11-DPA-713), has been described that binds to TSPO with high affinity. Here, we report the first examination of C-11-DPA-713 in human subjects using PET. Methods: Five healthy controls were studied with PET for 90 min after a bolus injection of high-specific-activity C-11-DPA-713. For comparison, 2 additional healthy controls were studied with C-11-R-PK11195. Arterial blood sampling and metabolite analysis were performed to allow the accurate quantification of tracer kinetics. Tracer uptake was evaluated for several brain regions. Tissue time-activity curves were fitted using 1- and 2-tissue-compartment-models, with goodness-of-fit tests showing a preference for the 2-tissue model. Results: In the healthy brain, the average plasma-to-tissue clearance and the total volume of distribution were an order of magnitude larger than measured for C-11-R-PK11195. Accordingly, dose-normalized time -activity curves showed that C-11-DPA-713 gives a larger brain signal. Conclusion: Studies in patient populations will help determine whether C-11-DPA-713 provides better sensitivity for evaluating increased TSPO expression. This initial study in humans shows that C-11-DPA-713 is a promising ligand for evaluating TSPO binding with PET.