Mapping Kappa Opioid Receptor Binding in Titi Monkeys with [¹¹C]GR103545 PET.

IF 2.4 4区医学 Q3 BIOCHEMICAL RESEARCH METHODS

Molecular Imaging Pub Date : 2025-05-11 eCollection Date: 2025-01-01 DOI:10.1177/15353508251341082

Alita Jesal D Almeida, Brad A Hobson, Logan E Savidge, Claudia Manca, John P Paulus, Karen L Bales, Abhijit J Chaudhari

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引用次数: 0

Abstract

Purpose: The kappa opioid receptor (KOR) plays a pivotal role in stress- and anxiety-related behaviors, with growing evidence linking it to stress induced by social isolation and separation. Despite this, tools for studying KOR in clinically relevant social contexts remain limited. The socially monogamous coppery titi monkey offers a translational model for investigating pair bonding. This study evaluated the feasibility of [¹¹C]GR103545 PET imaging to characterize KOR activity in vivo, and its pharmacological blockade for the first time in titi monkeys.

Methods: Adult titi monkeys (N = 6) underwent [¹¹C]GR103545 PET brain scans at baseline and following administration of the KOR antagonist CERC-501. Non-displaceable binding potential (BP_ND) was calculated across 14 brain volumes of interest (VOIs) implicated in social bonding, using Simplified and Logan reference tissue models (SRTM and LRTM), with the cerebellum as the reference region.

Results: Baseline [¹¹C]GR103545 uptake patterns across VOIs were consistent with reports in humans, other primates and published autoradiography data. CERC-501 pretreatment significantly reduced BP_ND (SRTM: 55.99%, LRTM: 59.68%) across several, but not all brain VOIs.

Conclusions: This study establishes [¹¹C]GR103545 PET as a viable tool for assessing KOR binding dynamics in titi monkeys, providing new opportunities to explore KOR modulation in social bonding and separation.

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用[11C]GR103545 PET定位Titi猴Kappa阿片受体结合

目的：kappa阿片受体（KOR）在压力和焦虑相关行为中起着关键作用，越来越多的证据表明它与社会孤立和分离引起的压力有关。尽管如此，在临床相关的社会背景下研究KOR的工具仍然有限。社会一夫一妻制的铜titi猴为研究配对关系提供了一个翻译模型。本研究首次在titi猴中评估了[11C]GR103545 PET成像在体内表征KOR活性的可行性，以及其药理阻断作用。方法：成年山猴（N = 6）在基线和给予KOR拮抗剂CERC-501后进行[11C]GR103545 PET脑部扫描。使用简化和Logan参考组织模型（SRTM和LRTM），以小脑为参考区域，计算了涉及社会联系的14个兴趣脑体积（VOIs）的不可置换结合电位（BPND）。结果：voi的基线[11C]GR103545摄取模式与人类、其他灵长类动物和已发表的放射自显影数据一致。CERC-501预处理显著降低了部分脑voi的BPND (SRTM: 55.99%, LRTM: 59.68%)，但不是所有脑voi。结论：本研究建立了[11C]GR103545 PET作为评估titi猴KOR结合动力学的可行工具，为探索KOR在社会结合和分离中的调节提供了新的机会。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Imaging Biochemistry, Genetics and Molecular Biology-Biotechnology

自引率

3.60%

发文量

期刊介绍： Molecular Imaging is a peer-reviewed, open access journal highlighting the breadth of molecular imaging research from basic science to preclinical studies to human applications. This serves both the scientific and clinical communities by disseminating novel results and concepts relevant to the biological study of normal and disease processes in both basic and translational studies ranging from mice to humans.