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Open Access 09-05-2024 | Naloxone | Original Article

Total-body imaging of mu-opioid receptors with [11C]carfentanil in non-human primates

Authors: Chia-Ju Hsieh, Catherine Hou, Hsiaoju Lee, Cosette Tomita, Alexander Schmitz, Konstantinos Plakas, Jacob G. Dubroff, Robert H. Mach

Published in: European Journal of Nuclear Medicine and Molecular Imaging

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Abstract

Purpose

Mu-opioid receptors (MORs) are widely expressed in the central nervous system (CNS), peripheral organs, and immune system. This study measured the whole body distribution of MORs in rhesus macaques using the MOR selective radioligand [11C]carfentanil ([11C]CFN) on the PennPET Explorer. Both baseline and blocking studies were conducted using either naloxone or GSK1521498 to measure the effect of the antagonists on MOR binding in both CNS and peripheral organs.

Methods

The PennPET Explorer was used for MOR total-body PET imaging in four rhesus macaques using [11C]CFN under baseline, naloxone pretreatment, and naloxone or GSK1521498 displacement conditions. Logan distribution volume ratio (DVR) was calculated by using a reference model to quantitate brain regions, and the standard uptake value ratios (SUVRs) were calculated for peripheral organs. The percent receptor occupancy (%RO) was calculated to establish the blocking effect of 0.14 mg/kg naloxone or GSK1521498.

Results

The %RO in MOR-abundant brain regions was 75–90% for naloxone and 72–84% for GSK1521498 in blocking studies. A higher than 90% of %RO were observed in cervical spinal cord for both naloxone and GSK1521498. It took approximately 4–6 min for naloxone or GSK1521498 to distribute to CNS and displace [11C]CFN from the MOR. A smaller effect was observed in heart wall in the naloxone and GSK1521498 blocking studies.

Conclusion

[11C]CFN total-body PET scans could be a useful approach for studying mechanism of action of MOR drugs used in the treatment of acute and chronic opioid use disorder and their effect on the biodistribution of synthetic opioids such as CFN. GSK1521498 could be a potential naloxone alternative to reverse opioid overdose.
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Metadata
Title
Total-body imaging of mu-opioid receptors with [11C]carfentanil in non-human primates
Authors
Chia-Ju Hsieh
Catherine Hou
Hsiaoju Lee
Cosette Tomita
Alexander Schmitz
Konstantinos Plakas
Jacob G. Dubroff
Robert H. Mach
Publication date
09-05-2024
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-024-06746-2