Initial evaluation of 11C-DPA-713, a novel TSPO PET ligand, in humans

Abstract

Translocator protein (TSPO) is upregulated in activated microglia and thus can serve as a marker of neuroinflammation. Recently, a novel radioligand, 11C-N,N-diethyl-2-[2-(4-methoxyphenyl)-5,7-dimethyl-pyrazolo[1,5-a] pyrimidin-3-yl]-acetamide (11C-DPA-713), has been described that binds to TSPO with high affinity. Here, we report the first examination of 11C-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 11C-DPA-713. For comparison, 2 additional healthy controls were studied with 11C-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-compartmentmodels, with goodness-of-fit tests showing a preference for the 2-tissuemodel. 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 11C-R-PK11195.Accordingly, dose-normalized time-activity curves showed that 11C-DPA-713 gives a larger brain signal. Conclusion: Studies in patient populationswill help determine whether 11C-DPA-713 provides better sensitivity for evaluating increased TSPO expression. This initial study in humans shows that 11C-DPA-713 is a promising ligand for evaluating TSPO binding with PET. COPYRIGHT © 2009 by the Society of Nuclear Medicine, Inc.