Staley J K, Van Dyck C H, Tan P Z, Al Tikriti M, Ramsby Q, Klump H, Ng C, Garg P, Soufer R, Baldwin R M, Innis R B
Department of Psychiatry, Yale University School of Medicine and VA Connecticut Healthcare System, 06516, West Haven, CT 06516, USA.
Nucl Med Biol. 2001 Apr;28(3):271-9. doi: 10.1016/s0969-8051(00)00212-2.
The regional distribution in brain, distribution volumes, and pharmacological specificity of the PET 5-HT(2A) receptor radiotracer [(18)F]deuteroaltanserin were evaluated and compared to those of its non-deuterated derivative [(18)F]altanserin. Both radiotracers were administered to baboons by bolus plus constant infusion and PET images were acquired up to 8 h. The time-activity curves for both tracers stabilized between 4 and 6 h. The ratio of total and free parent to metabolites was not significantly different between radiotracers; nevertheless, total cortical R(T) (equilibrium ratio of specific to nondisplaceable brain uptake) was significantly higher (34-78%) for [(18)F]deuteroaltanserin than for [(18)F]altanserin. In contrast, the binding potential (Bmax/K(D)) was similar between radiotracers. [(18)F]Deuteroaltanserin cortical activity was displaced by the 5-HT(2A) receptor antagonist SR 46349B but was not altered by changes in endogenous 5-HT induced by fenfluramine. These findings suggest that [(18)F]deuteroaltanserin is essentially equivalent to [(18)F]altanserin for 5-HT(2A) receptor imaging in the baboon.
评估了正电子发射断层扫描（PET）5-羟色胺（5-HT）2A受体放射性示踪剂[（18）F]氘代阿坦色林在大脑中的区域分布、分布容积和药理学特异性，并将其与非氘代衍生物[（18）F]阿坦色林进行比较。两种放射性示踪剂均通过静脉推注加持续输注的方式给予狒狒，并采集长达8小时的PET图像。两种示踪剂的时间-活性曲线在4至6小时之间稳定。两种放射性示踪剂之间母体与代谢物的总量和游离量之比无显著差异；然而，[（18）F]氘代阿坦色林的总皮质R（T）（特异性与不可置换性脑摄取的平衡比）比[（18）F]阿坦色林显著更高（34-78%）。相反，两种放射性示踪剂之间的结合潜力（Bmax/K（D））相似。[（18）F]氘代阿坦色林的皮质活性被5-HT2A受体拮抗剂SR 46349B取代，但未因芬氟拉明诱导的内源性5-HT变化而改变。这些发现表明，在狒狒中，[（18）F]氘代阿坦色林在5-HT2A受体成像方面与[（18）F]阿坦色林基本等效。
