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

以4-氟苯基卤化物为原料，合成了一种新型的用于组胺113受体显影的新型正电子放射配体--3-(1H-咪唑-4-基)丙基4-氟苯甲醚，并对其与受体的亲和力和选择性进行了初步评价。通过4-三甲基氨基苯甲醛三氟酸盐上的芳香族亲核取代氟化物，首先保留在C18柱上，并在那里通过流动NaBH；4-4-[^&lt；18&gt；F]氟苯甲醇水溶液有效地还原为4-[^&lt；18&gt；F]氟苯甲醇；用P_2I_4或Ph_3Pbr_2在GH_2Cl_2中反应，在40ﾟC下，用P_2I_4和Ph_3Pbr_2几乎定量地在室温下进行了快速的转化，放化产率接近90%。用这种试剂，在距EOB 30 mm的范围内得到了45-[‘8F]氟苄溴。该方法有望用于从氟化物中自动合成4-[^&lt；18&gt；F]氟化苯甲醚。以四氟化银为原料，在温和的反应条件下，以25%左右的放化产率合成了18-三甲基-氟丙烷。粗产物用硅胶柱纯化，然后用50%的HCOOH水解制得[18F]氟丙烷，EOB在2小时内以10%的放化总产率得到[18F]氟丙烷。[18F]氟丙烷与大鼠前脑膜的结合是立体选择性的、饱和的、可逆的和温度依赖的。将6-羟基多巴胺注射到黑质后，大鼠脑内的神经递质也增加。这些数据表明，[^&lt；18&gt；F]氟丙烷是一种潜在的用于多巴胺能去神经诱发的“超敏”成像的配体。

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.