11C-DPA-713 has much greater specific binding to translocator protein 18 kDa (TSPO) in human brain than 11C-(R)-PK11195. Issue 3 (March 2018)

• Record Type: Journal Article
• Authors: Kobayashi, Masato; Jiang, Teresa; Telu, Sanjay; Zoghbi, Sami S; Gunn, Roger N; Rabiner, Eugenii A; Owen, David R; Guo, Qi; Pike, Victor W; Innis, Robert B; Fujita, Masahiro
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 38:Issue 3(2018)
• Page Start: 393
• Page End: 403
• Publication Date: 2018-03
• Subjects: 18 kDa (TSPO) -- positron emission tomography -- rs6971 polymorphism -- XBD173 -- metabolite-corrected arterial input; Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1177/0271678X17699223
• Languages: English
• ISSNs: 0271-678X

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.