Dataset Information

Evaluation of Specific Binding of [¹¹C]RTI-97 to Kappa Opioid Receptor by Autoradiography and PET Imaging in Rat.

ABSTRACT: 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 labeled 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 cerebral uptake, the overall results showed a 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.

SUBMITTER: Fillesoye F

PROVIDER: S-EPMC8591749 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Evaluation of Specific Binding of [11C]RTI-97 to Kappa Opioid Receptor by Autoradiography and PET Imaging in Rat.

Fillesoye Fabien F Ibazizène Méziane M Marie Nicolas N Noble Florence F Perrio Cécile C

ACS medicinal chemistry letters 20211019 11

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 labeled 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 autoradiogra ...[more]

PMID: 34795862

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Project description:BackgroundIn molecular imaging with dynamic PET, the binding and dissociation of a targeted tracer is characterized by kinetics modeling which requires the arterial concentration of the tracer to be measured accurately. Once in the body the radiolabeled parent tracer may be subjected to hydrolysis, demethylation/dealkylation and other biochemical processes, resulting in the production and accumulation of different metabolites in blood which can be labeled with the same PET radionuclide as the parent. Since these radio-metabolites cannot be distinguished by PET scanning from the parent tracer, their contribution to the arterial concentration curve has to be removed for the accurate estimation of kinetic parameters from kinetic analysis of dynamic PET. High-performance liquid chromatography has been used to separate and measure radio-metabolites in blood plasma; however, the method is labor intensive and remains a challenge to implement for each individual patient. The purpose of this study is to develop an alternate technique based on thin layer chromatography (TLC) and a sensitive commercial autoradiography system (Beaver, Ai4R, Nantes, France) to measure radio-metabolites in blood plasma of two targeted tracers-[18F]FAZA and [18F]FEPPA, for imaging hypoxia and inflammation, respectively.ResultsRadioactivity as low as 17 Bq in 2 µL of pig's plasma can be detected on the TLC plate using autoradiography. Peaks corresponding to the parent tracer and radio-metabolites could be distinguished in the line profile through each sample (n = 8) in the autoradiographic image. Significant intersubject and intra-subject variability in radio-metabolites production could be observed with both tracers. For [18F]FEPPA, 50% of plasma activity was from radio-metabolites as early as 5-min post injection, while for [18F]FAZA, significant metabolites did not appear until 50-min post. Simulation study investigating the effect of radio-metabolite in the estimation of kinetic parameters indicated that 32-400% parameter error can result without radio-metabolites correction.ConclusionTLC coupled with autoradiography is a good alternative to high-performance liquid chromatography for radio-metabolite correction. The advantages of requiring only small blood samples (~ 100 μL) and of analyzing multiple samples simultaneously, make the method suitable for individual dynamic PET studies.

Dataset Information

Evaluation of Specific Binding of [¹¹C]RTI-97 to Kappa Opioid Receptor by Autoradiography and PET Imaging in Rat.

Publications

Evaluation of Specific Binding of [<sup>11</sup>C]RTI-97 to Kappa Opioid Receptor by Autoradiography and PET Imaging in Rat.

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