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

Title: (11)C-DPA-713 has much greater specific binding to translocator protein 18 kDa (TSPO) in human brain than (11)C-( R)-PK11195
Author(s): Kobayashi, M
Jiang, T
Telu, S
Zoghbi, SS
Gunn, RN
Rabiner, EA
Owen, DR
Guo, Q
Pike, VW
Innis, RB
Fujita, M
Item Type: Journal Article
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 ( BPND)) 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 BPND 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.
Publication Date: 21-Mar-2017
Date of Acceptance: 13-Jan-2017
URI: http://hdl.handle.net/10044/1/51601
DOI: https://dx.doi.org/10.1177/0271678X17699223
ISSN: 1559-7016
Publisher: SAGE Publications
Start Page: 393
End Page: 403
Journal / Book Title: Journal of Cerebral Blood Flow and Metabolism
Volume: 38
Issue: 3
Sponsor/Funder: Medical Research Council (MRC)
Medical Research Council (MRC)
Funder's Grant Number: MR/N008219/1
MR/N026934/1
Copyright Statement: © Sage 2017. The final publication is available via Sage at http://dx.doi.org/10.1177/0271678X17699223
Keywords: 18 kDa (TSPO)
XBD173
metabolite-corrected arterial input
positron emission tomography
rs6971 polymorphism
18 kDa (TSPO)
XBD173
metabolite-corrected arterial input
positron emission tomography
rs6971 polymorphism
1103 Clinical Sciences
1109 Neurosciences
1102 Cardiovascular Medicine And Haematology
Neurology & Neurosurgery
Publication Status: Published
Appears in Collections:Department of Medicine
Faculty of Medicine



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