Whole-body biodistribution of the cannabinoid type 1 receptor ligand [18F]MK-9470 in the rat
Whole-body biodistribution of the cannabinoid type 1 receptor ligand [18F]MK-9470 in the rat
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DOI：
10.1016/j.nucmedbio.2017.06.003
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发表时间：
2017-09-01
影响因子：
3.1
通讯作者：
Miederer, I.
中科院分区：
文献类型：
--
作者：
Buchholz, H. G.;Uebbing, K.;Miederer, I.
内源性大麻素系统参与体内的许多过程，包括记忆、奖赏、疼痛、运动活动、食物摄入、能量代谢和胃肠道功能。 [F-18]MK-9470 是一种正电子发射断层扫描 (PET) 配体，能够以高亲和力和选择性与 1 型大麻素受体结合。为了充分表征配体行为，将使用体内 microPET 测量的示踪剂摄取与离体组织解剖的结果进行比较。将 12 只雄性 Sprague-Dawley 大鼠分为三个亚组，并使用 PET 在 10 分钟、30 分钟和 90 分钟的时间段内进行扫描。随后，一些动物的器官被解剖。放射性的吸收以％1D/ml和％ID/(g组织)表示。为了比较体内和离体方法，计算了 Bland Altman 图。 [F-18]MK-9470 的最高摄取出现在肝脏和小肠中；大脑显示出较少的吸收，而在心脏、肺、肾和骨骼组织中观察到低且非特异性的结合。在大脑中，[F-18]MK-9470 的标准化摄取平均为 0.25%ID/ml（范围：0.16 至 0.28%ID/ml）。 Bland-Altman 图揭示了 90 分钟采集方案的方法之间的最佳一致性。[F-18]MK-9470 的高肝脏积聚和代谢主要通过肠内排泄发生，随着时间的推移可能会发生很大变化，这一发现可能与定量脑研究中的代谢物测定相关。体内和离体方法之间的比较表明，使用正电子发射断层扫描进行 [F-18]MK-9470 的全身分布是离体生物分布的更好替代方案，并且需要的动物数量明显较少。 (C) 2017 Elsevier Inc. 保留所有权利。
The endocannabinoid system participates in many processes in the body, including memory, reward, pain, motor activity, food intake, energy metabolism, and gastrointestinal functions. [F-18]MK-9470 is a positron emission tomography (PET) ligand that binds with high affinity and selectivity to the cannabinoid type 1 receptor. In order to fully characterize ligand behavior, tracer uptake measured using in vivo microPET was compared with results from ex vivo tissue dissection.Twelve male Sprague-Dawley rats were divided into three subgroups and scanned over time periods of 10 min, 30 min and 90 min using PET. Afterwards, a number of the animals' organs were dissected. Uptake of radioactivity was expressed in terms of %1D/ml and %ID/(g tissue). For comparison of in vivo and ex vivo methods, Bland Altman plots were computed.The highest uptake of [F-18]MK-9470 was found in the liver and small intestine; the brain showed less uptake, while low and unspecific binding was observed in tissue of the heart, lung, kidney and bone. In the brain, normalized uptake of [F-18]MK-9470 was on average 0.25%ID/ml (range: 0.16 to 0.28%ID/ml). Bland-Altman plots revealed the best agreement between methods for the 90 min acquisition protocols.High hepatic accumulation and metabolism of [F-18]MK-9470 occur with mainly enteral excretion, which may vary considerably over time a finding which may be of relevance in metabolite determination in quantitative brain studies. Comparisons between in vivo and ex vivo methods showed that whole-body distribution of [F-18]MK-9470 using positron emission tomography is a preferable alternative to ex vivo biodistribution, and requires a significantly smaller number of animals. (C) 2017 Elsevier Inc. All rights reserved.