Wilson A A, DaSilva J N, Houle S
Pet Centre, Clarke Institute of Psychiatry, Toronto, On, Canada.
Nucl Med Biol. 1996 Feb;23(2):141-6. doi: 10.1016/0969-8051(95)02044-6.
Four analogues of the potent dopamine transporter ligand, WIN 35,428, were radiolabelled with 11C and 18F at the 2-beta-carboxy position for evaluation as potential ligands for imaging dopamine uptake sites by positron emission tomography (PET) namely, methyl (1R-2-exo-3-exo)-8- methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate (RTI-32), its 4-chlorophenyl analogue (RTI-31), 2'-fluoroethyl (1R-2-exo-3-exo)-8-methyl-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2 - carboxylate (FETT) and its 4-chlorophenyl analogue (FECT). Upon intravenous injection in rats, all four radiotracers displayed preferential accumulation of radioactivity in regions known to contain high concentrations of dopamine uptake sites. Competition studies with two of the analogues, [11C]RTI-32 and [18F]FETT, demonstrated that, for both radiotracers, binding was saturable and displayed the appropriate pharmacology as potential PET ligands for imaging the dopamine transporter. Striatum to cerebellar ratios for [11C]RTI-32 (at 90 min post-injection) and [18F]FETT (at 120 min post-injection) were 27 and 21, respectively.
强效多巴胺转运体配体WIN 35,428的四种类似物在2-β-羧基位置用11C和18F进行放射性标记，以评估其作为正电子发射断层扫描（PET）成像多巴胺摄取位点的潜在配体，即甲基(1R-2-exo-3-exo)-8-甲基-3-(4-甲基苯基)-8-氮杂双环[3.2.1]辛烷-2-羧酸盐（RTI-32）、其4-氯苯基类似物（RTI-31）、2'-氟乙基(1R-2-exo-3-exo)-8-甲基-3-(4-甲基苯基)-8-氮杂双环[3.2.1]辛烷-2-羧酸盐（FETT）及其4-氯苯基类似物（FECT）。在大鼠静脉注射后，所有四种放射性示踪剂在已知含有高浓度多巴胺摄取位点的区域均显示出放射性的优先积累。用其中两种类似物[11C]RTI-32和[18F]FETT进行的竞争研究表明，对于这两种放射性示踪剂，结合是可饱和的，并显示出作为成像多巴胺转运体的潜在PET配体的适当药理学特性。[11C]RTI-32（注射后90分钟）和[18F]FETT（注射后120分钟）的纹状体与小脑的比值分别为27和21。
