Evaluation of Specific Binding of [11C]RTI-97 to KOR by Autoradiog-raphy and PET Imaging in Rat

Fabien Fillesoye (1) , Méziane Ibazizene (1) , Nicolas Marie (2) , Florence Noble (2) , Cécile Perrio (3)

1 LDM-TEP - Laboratoire de Développements Méthodologiques en Tomographie par Emission de Positons
2 T3S - UMR_S 1124 - Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire
3 ISTCT - Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales

Kappa opioid receptor (KOR) PET imaging remains attractive to understand the role of KOR in health and diseases, and to help the development of drugs especially for psychiatric disorders such as depression, anxiety and addiction. The potent and selective KOR antagonist RTI-97 labelled with carbon-11 was previously demonstrated to display specific KOR binding in mouse brain by ex vivo autoradiography studies. Herein, we evaluated [11C]RTI-97 in rat by in vitro autoradiography and by in vivo PET imaging. The radiosynthesis of [11C]RTI-97 was optimized to obtain high molar activities. Despite a low cer-ebral uptake, the overall results showed an heterogeneous repartition and specific KOR binding of [11C]RTI-97 in brain, and a high and specific accumulation of [11C]RTI-97 in pituitary in accordance with KOR expression.

Mots clés: Kappa opioid receptor; RTI-97; JDTic; carbon-11; autoradiography; positron emission tomography

Domaines: Chimie; Sciences du Vivant [q-bio]

Fabien Fillesoye, Méziane Ibazizene, Nicolas Marie, Florence Noble, Cécile Perrio. Evaluation of Specific Binding of [11C]RTI-97 to KOR by Autoradiog-raphy and PET Imaging in Rat. ACS Medicinal Chemistry Letters, 2021, 12 (11), pp.1739-1744. ⟨10.1021/acsmedchemlett.1c00369⟩. ⟨hal-03381883⟩