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Determination of [(11)C]PBR28 binding potential in vivo: a first human TSPO blocking study.

journal contribution
posted on 2023-06-09, 17:56 authored by David R Owen, Qi Guo, Nicola J Kalk, Alessandro ColasantiAlessandro Colasanti, Dimitra Kalogiannopoulou, Rahul Dimmer, Yvonne L Lewis, Vincenzo Libri, Julien Barletta, Joaquim Ramada-Magalhaes, Aruloly Kamalakaran, David J Nutt, Jan Passchier, Paul M Matthews, Roger N Gunn, Eugenii A Rabiner
Positron emission tomography (PET) targeting the 18?kDa translocator protein (TSPO) is used to quantify neuroinflammation. Translocator protein is expressed throughout the brain, and therefore a classical reference region approach cannot be used to estimate binding potential (BPND). Here, we used blockade of the TSPO radioligand [(11)C]PBR28 with the TSPO ligand XBD173, to determine the non-displaceable volume of distribution (VND), and hence estimate the BPND. A total of 26 healthy volunteers, 16 high-affinity binders (HABs) and 10 mixed affinity binders (MABs) underwent a [(11)C]PBR28 PET scan with arterial sampling. Six of the HABs received oral XBD173 (10 to 90?mg), 2?hours before a repeat scan. In XBD173-dosed subjects, VND was estimated via the occupancy plot. Values of BPND for all subjects were calculated using this VND estimate. Total volume of distribution (VT) of MABs (2.94±0.31) was lower than VT of HABs (4.33±0.29) (P<0.005). There was dose-dependent occupancy of TSPO by XBD173 (ED50=0.34±0.13?mg/kg). The occupancy plot provided a VND estimate of 1.98 (1.69, 2.26). Based on these VND estimates, BPND for HABs is approximately twice that of MABs, consistent with predictions from in vitro data. Our estimates of [(11)C]PBR28 VND and hence BPND in the healthy human brain are consistent with in vitro predictions. XBD173 blockade provides a practical means of estimating VND for TSPO targeting radioligands.

History

Publication status

  • Published

File Version

  • Published version

Journal

Journal of Cerebral Blood Flow and Metabolism

ISSN

0271-678X

Publisher

Lippincott, Williams & Wilkins

Issue

6

Volume

34

Page range

989-994

Department affiliated with

  • BSMS Neuroscience Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2019-05-31

First Open Access (FOA) Date

2019-05-31

First Compliant Deposit (FCD) Date

2019-05-31

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