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

Christopher J. Endres, Martin G. Pomper, Michelle James, Ovsev Uzuner, Dima A. Hammoud, Crystal C. Watkins, Aaron Reynolds, John Hilton, Robert F. Dannals, Michael Kassiou

Research output: Contribution to journalArticle

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

Original languageEnglish (US)
Pages (from-to)1276-1282
Number of pages7
JournalJournal of Nuclear Medicine
Volume50
Issue number8
DOIs
StatePublished - Aug 1 2009

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Keywords

  • Compartmental analysis
  • Microglia
  • Positron emission tomography
  • Translocator protein

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Endres, C. J., Pomper, M. G., James, M., Uzuner, O., Hammoud, D. A., Watkins, C. C., Reynolds, A., Hilton, J., Dannals, R. F., & Kassiou, M. (2009). Initial evaluation of 11C-DPA-713, a novel TSPO PET ligand, in humans. Journal of Nuclear Medicine, 50(8), 1276-1282. https://doi.org/10.2967/jnumed.109.062265