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

以4-[^<18>F]氟酰卤化物为原料，成功制备了一种新的、有用的正电子放射配体[^<18>F]氟proxyfan （3-（h -咪唑-4-基）丙基4-[^<18>F]氟苯醚），用于组胺113受体的显像，并初步评价了其对受体的亲和力和选择性。用4-三甲胺苯甲醛三氟酸盐对[^<18>F]氟化物进行芳香亲核取代合成的4-[^<18>F]氟苯甲醛，首先保留在C18滤筒上，然后通过NaBH_<4-> 4-[^<18>F]水溶液流动，有效地还原为4-[^<18>F]氟苯甲醇，在GH_2Cl_2中使用P_2I_4或Ph_3PBr_2有效地转化为4-[^<18>F]氟苯甲醇。用Ph_3PBr_2（室温）制备的4-['8F]氟溴化试剂在离EOB 30 mm范围内的总放射化学收率为45-55%。该方法有望适用于由[^<18>F]氟化物自动制备4-[^<18>F]氟苄基卤化物。[^<18>F]在温和的反应条件下，以4-[^<18>F]氟苄基溴为原料，用三氟化银以约25%的放射化学产率合成了三烷基氟丙醚。粗产物用硅胶筒纯化，然后用50%的HCOOH水解成[^<18>F]氟丙烷。[^<18>F]在2小时内从EOB获得了总放射化学产率10%的氟丙醚。[^<18>F]氟代理木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。黑质注射6-羟多巴胺后，大鼠脑内的多巴胺含量也有所增加。这些数据表明[^<18>F]氟代理木是一种潜在的配体，用于多巴胺能去神经控制诱导的成像“超敏感”。

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.