The development of a new radioligand having a [^<18>F] fluorobenzyl group for functional imaging of neurotransmitters by PET.

开发具有[^ 18 F]氟苄基的新放射性配体，用于通过PET对神经递质进行功能成像。

• 批准号: 09670913
• 负责人: IWATA Ren
• 金额: $ 1.92万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670913/
• 关键词: Histamine receptor; Fluorobenzyl halide; positron emitter; PET; Radiopharmaceutical; Fluorine-18; Fluoroproxyfan; Radioligand

A new, useful positron emitting radioligand, [^<18>F]fluoroproxyfan (3-(1H-Imidazol-4-yl)propyl 4-[^<18>F]fluorobenzyl ether), was successfully prepared from 4-[^<18>F]fluorobenzyl halide for imaging of histamine 113 receptors and preliminarily evaluated for its affinity and selectivity to the receptors.4-[^<18>F]Fluorobenzaldehyde, synthesized from [^<18>F]fluoride by aromatic nucleophilic substitution on 4-trimethylammoniumbenzaldehyde triflate, was first retained on a C18 cartridge and there efficiently reduced to 4-[^<18>F]fluorobenzyl alcohol simply by flowing an aqueous solution of NaBH_<4-> 4-[^<18>F]Fluorobenzyl alcohol was efficiently converted to 4-[^<18>F]fluorobenzyl halide using P_2I_4 or Ph_3PBr_2 in GH_2Cl_2. The conversion rapidly proceeded in radiochemical yields of nearly 90% at 40ﾟC with P_2I4 and almost quantitatively at room temperature with Ph_3PBr_2- With this last reagent 4-['8F]fluorobenzyl bromide was obtained in overall radiochemical yields of 45-55% within 30 mm from EOB.This method is expected to be suitable for automated preparation of 4-[^<18>F]fluorobenzyl halides from [^<18>F]fluoride.[^<18>F]Trityl-fluoroproxyfan was synthesized in around 25% radiochemical yields from 4-[^<18>F]fluoro-benzyl bromide using silver triflate under mild reaction conditions. The crude product was purified with a silica gel cartridge and then hydrolyzed into [^<18>F]fluoroproxyfan with 50% HCOOH.[^<18>F]Fluoroproxyfan was obtained in 10% overall radiochemical yields within 2 hrs from EOB.The binding of [^<18>F]fiuoroproxyfan to the membranes of rat forebrain was found to be stereoselective, saturable, reversible and temperature-dependent. it was also increased in the rat brain following 6-hydroxydopamine injection to substantia nigra. These data suggest that [^<18>F]fluoroproxyfan is a potential ligand for imaging "supersensitivity" induced by dopaminergic denervation.

以4-[^ F]氟苄基卤为原料，合成了一种新型的正电子放射性配体[^<18>F]氟丙氧基凡（3-（1H-咪唑-4-基）丙基4-[^<18>F]氟苄基醚）<18>，并初步评价了其对组胺113受体的亲和性和选择性<18><18><18><4-><18><18>。用P_2I_4和Ph_3PBr_2在40 ℃和室温下进行快速转化，放化产率分别接近90%和90%。用后一种试剂，在离EOB 30 mm的距离内，总放化产率为45-55%<18><18>。在<18>温和的反应条件下，使用三氟甲磺酸银从4-[^ F]氟苄基溴以约25%的放射化学产率合成[^ F]三苯甲基-氟丙烷<18>。将粗产物用硅胶柱纯化，然后用50%HCOOH水解成[13 <18>F]氟丙醚。[~<18>（13）F]氟丙<18>凡与大鼠前脑膜的结合具有立体选择性、饱和性、可逆性和温度依赖性。在向黑质注射6-羟基多巴胺后，其在大鼠脑中也增加。这些数据表明，<18>氟丙芬是一个潜在的配体成像“超敏反应”诱导多巴胺能神经支配。