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首页> 外文期刊>European Journal of Medicinal Chemistry: Chimie Therapeutique >Synthesis, evaluation and metabolic studies of radiotracers containing a 4-(4-(18F)-fluorobenzyl)piperidin-1-yl moiety for the PET imaging of NR2B NMDA receptors.
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Synthesis, evaluation and metabolic studies of radiotracers containing a 4-(4-(18F)-fluorobenzyl)piperidin-1-yl moiety for the PET imaging of NR2B NMDA receptors.

机译：包含4-（4-（18F）-氟苄基）哌啶-1-基部分的放射性示踪剂的合成，评估和代谢研究，用于NR2B NMDA受体的PET成像。

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摘要

In this study, novel specific PET radioligands containing the 4-(4-fluorobenzyl)piperidine moiety and selectively antagonistic for the NR2B subunit containing NMDA receptors were developed. Two antagonists, RGH-896 (1a) and 4-(4-fluorobenzyl)piperidinyl-1-methyl-2-benzimidazol-5-ol (2a), belonging to two different structural families, were radiolabeled by an aromatic nucleophilic radiofluorination followed by a reduction of the para-position carbonyl function. Radiotracers [18F]1a, [18F]2a or the pattern 4-(4-[18F]-fluorobenzyl)piperidine ([18F]6) demonstrated an identical in vivo behavior with high accumulation of radioactivity in bone and cartilage which would suggest a radiodefluorination of the radiotracers. The identification of metabolites from 6 by LC-MS-MS confirmed the significant degree of defluorination as a result of the in vivo hydroxylation in the benzyl ring. In conclusion, [18F]1a or [18F]2a are not suitable for imaging the NR2B NMDA receptors due to their poor brain penetration. We also argue for a cautious use of the radiolabeled pattern, 4-(4-[18F]-fluorobenzyl)piperidine, to develop PET radiotracers.
机译：在这项研究中，开发了包含4-（4-氟苄基）哌啶部分并选择性拮抗NMDA受体的NR2B亚基的新型特异性PET放射性配体。属于两个不同结构家族的两个拮抗剂RGH-896（1a）和4-（4-氟苄基）哌啶基-1-甲基-2-苯并咪唑-5-醇（2a）通过芳族亲核性放射性氟化进行放射性标记对位羰基官能团的还原。放射性示踪剂[18F] 1a，[18F] 2a或模式4-（4- [18F]-氟苄基）哌啶（[18F] 6）表现出相同的体内行为，并在骨骼和软骨中具有高放射性积聚，表明存在放射性。放射性示踪剂的放射性脱氟。通过LC-MS-MS从6种代谢产物中鉴定出，由于体内苄基环中的羟基化作用，脱氟程度明显。总之，[18F] 1a或[18F] 2a由于其较差的脑部穿透性，因此不适合对NR2B NMDA受体进行成像。我们还主张谨慎使用放射性标记的图案4-（4- [18F]-氟苄基）哌啶来开发PET放射性示踪剂。

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