Moerlein S M, Laufer P, Stöcklin G, Pawlik G, Wienhard K, Heiss W D
Eur J Nucl Med. 1986;12(4):211-6. doi: 10.1007/BF00256924.
A comparative evaluation of three radiobrominated butyrophenone neuroleptics--bromospiperone (BSP), brombenperidol (BBP), and bromperidol (BP)--was made to assess the applicability of these compounds as radiopharmaceuticals labelled with the positron emitter 75Br (T1/2 = 1.6 h) for mapping cerebral dopaminergic receptor areas non-invasively with positron emission tomography (PET). BSP, BBP, and BP were prepared in high specific activities with high radiochemical yields, using electrophilic reactions with no-carrier-added 77Br- or 75Br-. Screening tests in rats using 77Br-labelled compounds indicated D2-specific localization for 77Br-BSP and 77Br-BBP, whereas PET experiments in baboons showed that only 75Br-BSP preferentially localized in cerebral tissues rich in dopaminergic receptors. The data suggest an inverse relationship between cerebral uptake and receptor-specific localization, which was attributed to a complicated interplay between the D2 receptor binding affinity, lipophilicity, % ionization and molecular weight of the radioligand, and the binding capacity of the cerebral tissues. 75Br-BSP gave a striatum-to-cerebellum ratio of 3 in baboon brain 5 h post-injection, which allowed visualization of dopaminergic-receptor-containing areas of the living brain using PET.
对三种放射性溴化丁酰苯类抗精神病药物——溴螺哌隆（BSP）、溴苯哌利多（BBP）和溴哌利多（BP）进行了比较评估，以评估这些化合物作为用正电子发射体75Br（半衰期=1.6小时）标记的放射性药物，通过正电子发射断层扫描（PET）对脑多巴胺能受体区域进行无创成像的适用性。使用无载体添加的77Br-或75Br-的亲电反应，以高放射性化学产率制备了高比活的BSP、BBP和BP。使用77Br标记化合物在大鼠中进行的筛选试验表明，77Br-BSP和77Br-BBP具有D2特异性定位，而在狒狒中进行的PET实验表明，只有75Br-BSP优先定位于富含多巴胺能受体的脑组织中。数据表明脑摄取与受体特异性定位之间呈负相关，这归因于放射性配体的D2受体结合亲和力、亲脂性、电离百分比和分子量与脑组织结合能力之间的复杂相互作用。注射后5小时，75Br-BSP在狒狒脑中的纹状体与小脑比值为3，这使得使用PET能够可视化活脑的含多巴胺能受体区域。
