Radiochemistry and Biomarker Development Unit, Department of Nuclear Medicine, Medical University of Vienna, Vienna, Austria; Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Vienna, Austria.
Nucl Med Biol. 2013 Oct;40(7):919-25. doi: 10.1016/j.nucmedbio.2013.05.010. Epub 2013 Jul 3.
Due to its involvement in a variety of pathologies (obesity, diabetes, gut inflammation and depression), the melanin concentrating hormone receptor 1 (MCHR1) is a new target for the treatment of these lifestyle diseases. We previously presented the radiosynthesis of [(11)C]SNAP-7941, the first potential PET tracer for the MCHR1.
We herein present its in vitro and in vivo evaluation, including binding affinity, plasma stability, stability against liver mircrosomes and carboxylesterase, lipohilicity, biodistribution, in vivo metabolism and small-animal PET.
[(11)C]SNAP-7941 evinced high stability against liver microsomes, carboxylesterase and in human plasma. The first small-animal PET experiments revealed a 5 fold increased brain uptake after Pgp/BCRP inhibition. Therefore, it can be assumed that [(11)C]SNAP-7941 is a Pgp/BCRP substrate. No metabolites were found in brain.
On the basis of these experiments with healthy rats, the suitability of [(11)C]SNAP-7941 for the visualisation of central and peripheral MCHR1 remains speculative.
由于其参与了多种病理学（肥胖、糖尿病、肠道炎症和抑郁症），黑色素浓缩激素受体 1（MCHR1）成为治疗这些生活方式疾病的新靶点。我们之前介绍了[(11)C]SNAP-7941 的放射性合成，这是用于 MCHR1 的首个潜在 PET 示踪剂。
我们在此介绍其体外和体内评估，包括结合亲和力、血浆稳定性、对肝微粒体和羧酸酯酶的稳定性、亲脂性、生物分布、体内代谢和小动物 PET。
[(11)C]SNAP-7941 对肝微粒体、羧酸酯酶和人血浆具有很高的稳定性。首次小动物 PET 实验显示，在 Pgp/BCRP 抑制后，脑摄取增加了 5 倍。因此，可以假设[(11)C]SNAP-7941 是 Pgp/BCRP 的底物。在脑内未发现代谢物。
基于这些健康大鼠的实验，[(11)C]SNAP-7941 用于可视化中枢和外周 MCHR1 的适用性仍存在争议。
