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.

一种新的、有用的正电子发射放射性配体，[^ 18 F]氟丙氧基凡（3-（1H-咪唑-4-基）丙基4-[^ 18 F]氟苄基醚），由4-[^成功制备。 18 F]氟苄基卤化物用于组胺113受体的成像并初步评价其对组胺113受体的亲和力和选择性4-[^ 18 F]氟苯甲醛，由[^ 18 F]氟化物通过4-三甲基苯甲醛三氟甲磺酸铵上的芳香族亲核取代合成，首先保留在C18柱上，并有效还原为4-[^< 18>F]氟苯甲醇，只需流过NaBH_<4->水溶液即可使用 P_2I_4 或 Ph_3PBr_2 在 GH_2Cl_2 中将 4-[^ 18 F]氟苄醇有效转化为 4-[^ 18 F]氟苄基卤。在 40℃下，使用 P_2I4 的转化快速进行，放射化学产率接近 90%。并在室温下用 Ph_3PBr_2- 使用最后一种试剂几乎定量在距离EOB 30mm内以45-55％的总放射化学产率获得4-['8F]氟苄基溴。该方法预计适用于从[^18F]氟苄基卤自动制备。 18 F]氟化物。[^ 18 F]三苯甲基-氟代丙苯以大约25％的放射化学产率合成自使用三氟甲磺酸银在温和的反应条件下得到4-[^ 18 F]氟-苄基溴。粗产物用硅胶柱纯化，然后用50％HCOOH水解成[^ 18 F]氟丙氧基苯。 18 F]Fluoroproxyfan在2小时内从EOB获得，总放射化学产率为10％。发现[^ 18 F]氟丙氧基苯对大鼠前脑膜具有立体选择性、可饱和性、可逆性和温度依赖性，在将6-羟基多巴胺注射到黑质后，其在大鼠脑中也有所增加。 18 F]氟丙醚是用于对由多巴胺能去神经支配诱导的“超敏性”进行成像的潜在配体。