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J Cereb Blood Flow Metab. 2018 Mar;38(3):393-403. doi: 10.1177/0271678X17699223. Epub 2017 Mar 21.

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

Author information

1
1 Molecular Imaging Branch, National Institute of Mental Health, National Institute of Health, Bethesda, MD, USA.
2
2 Imanova Ltd, London, UK.
3
3 Division of Brain Sciences, Department of Medicine, Imperial College, London, UK.

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 11C-( R)-PK11195 in human imaging. This study sought to quantitatively measure the "signal to background" ratio (assessed as binding potential ( BPND)) of 11C-( R)-PK11195 compared to one of the most promising second-generation radioligands, 11C-DPA-713. Healthy subjects had dynamic PET scans and arterial blood measurements of radioligand after injection of either 11C-( R)-PK11195 (16 subjects) or 11C-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). 11C-DPA-713 showed a significant sensitivity to genotype in brain, whereas 11C-( R)-PK11195 did not. Lassen occupancy plot analysis revealed that the specific binding of 11C-DPA-713 was much greater than that of 11C-( R)-PK11195. The BPND in high-affinity binders was about 10-fold higher for 11C-DPA-713 (7.3) than for 11C-( R)-PK11195 (0.75). Although the high specific binding of 11C-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.

KEYWORDS:

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

PMID:
28322082
PMCID:
PMC5851139
[Available on 2019-03-01]
DOI:
10.1177/0271678X17699223
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