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(11)C-DPA-713 has much greater specific binding to translocator protein 18 kDa (TSPO) in human brain than (11)C-( R)-PK11195
File | Description | Size | Format | |
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s1-ln25402255-1117307952-1939656818Hwf2067135197IdV-191380689025402255PDF_HI0001.pdf | Accepted version | 1.2 MB | Adobe PDF | View/Open |
Title: | (11)C-DPA-713 has much greater specific binding to translocator protein 18 kDa (TSPO) in human brain than (11)C-( R)-PK11195 |
Authors: | 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. |
Issue 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 |
Copyright Statement: | © Sage 2017. The final publication is available via Sage at http://dx.doi.org/10.1177/0271678X17699223 |
Sponsor/Funder: | Medical Research Council (MRC) Medical Research Council (MRC) |
Funder's Grant Number: | MR/N008219/1 MR/N026934/1 |
Keywords: | 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 (up to 2019) |