11 C-DPA-713 has much greater specific binding to translocator protein 18 kDa (TSPO) in human brain than 11 C-(R)-PK11195

Masato Kobayashi, Teresa Jiang, Sanjay Telu, Sami S. Zoghbi, Roger N. Gunn, Eugenii A. Rabiner, David R. Owen, Qi Guo, Victor W. Pike, Robert B. Innis, Masahiro Fujita

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Positron emission tomography (PET) radioligands for translocator protein 18 kDa (TSPO) are widely used to measure neuroinflammation, but controversy exists whether second-generation radioligands are superior to the prototypical agent 11 C-(R)-PK11195 in human imaging. This study sought to quantitatively measure the “signal to background” ratio (assessed as binding potential (BP ND )) of 11 C-(R)-PK11195 compared to one of the most promising second-generation radioligands, 11 C-DPA-713. Healthy subjects had dynamic PET scans and arterial blood measurements of radioligand after injection of either 11 C-(R)-PK11195 (16 subjects) or 11 C-DPA-713 (22 subjects). To measure the amount of specific binding, a subset of these subjects was scanned after administration of the TSPO blocking drug XBD173 (30–90 mg PO). 11 C-DPA-713 showed a significant sensitivity to genotype in brain, whereas 11 C-(R)-PK11195 did not. Lassen occupancy plot analysis revealed that the specific binding of 11 C-DPA-713 was much greater than that of 11 C-(R)-PK11195. The BP ND in high-affinity binders was about 10-fold higher for 11 C-DPA-713 (7.3) than for 11 C-(R)-PK11195 (0.75). Although the high specific binding of 11 C-DPA-713 suggests it is an ideal ligand to measure TSPO, we also found that its distribution volume increased over time, consistent with the accumulation of radiometabolites in brain.

Original languageEnglish (US)
Pages (from-to)393-403
Number of pages11
JournalJournal of Cerebral Blood Flow and Metabolism
Volume38
Issue number3
DOIs
StatePublished - Mar 1 2018

Keywords

  • 18 kDa (TSPO)
  • XBD173
  • metabolite-corrected arterial input
  • positron emission tomography
  • rs6971 polymorphism

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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