PET Department, CC/NIH, Bethesda, MD, USA.
Nucl Med Biol. 2012 Jan;39(1):45-55. doi: 10.1016/j.nucmedbio.2011.06.003. Epub 2011 Aug 9.
[(18)F]FP-TZTP is an M2 muscarinic subtype selective receptor-binding radiotracer used in vivo to image human and nonhuman primate brain following both bolus injection and infusion. In order to carry out repeated studies in rodents, the techniques developed for primates must be transferred to rodents with the same precision. This includes obtaining a metabolite-corrected input function.
We compared bolus injection with constant infusion in rats that were awake or under isoflurane anesthesia. Brain-plasma and brain-blood distribution ratios were calculated by dividing brain (18)F concentrations, determined in vivo by positron emission tomography imaging with the Advanced Technology Laboratory Animal Scanner, ex vivo by direct counting in excised brain tissue or by quantitative autoradiography by the plasma or whole blood concentrations that had been corrected for metabolite contents.
Blood volume constraints prevented adequate blood sampling to define a precise input function after bolus injection, thus preventing full kinetic analysis. Constant infusion, however, required fewer blood samples to define the input function, allowing calculation of distribution ratios, but complete equilibrium between plasma and tissue had not yet been reached after 120 min.
Our results showed that the blood clearance and metabolism were too rapid to obtain a reproducible input function after bolus injection. The equilibrium distribution ratios did not lead to precise biochemical parameters, but the constant infusion was more suitable in that distribution ratios between tissue and plasma were statistically more precise. Constant infusion is the better approach for studying [(18)F]FP-TZTP by small animal imaging.
[(18)F]FP-TZTP 是一种 M2 毒蕈碱亚型选择性受体结合放射性示踪剂，用于在静脉推注和输注后对人和非人灵长类动物的大脑进行体内成像。为了在啮齿动物中进行重复研究，必须将为灵长类动物开发的技术以相同的精度转移到啮齿动物中。这包括获得代谢校正的输入函数。
我们比较了清醒或异氟烷麻醉大鼠的静脉推注和恒速输注。脑-血浆和脑-血分配比通过将脑（18）F 浓度除以脑（18）F 浓度来计算，通过正电子发射断层扫描成像用先进技术实验室动物扫描仪在体内测定，通过直接计数切除脑组织中的放射性计数或通过定量放射自显影用校正代谢物含量的血浆或全血浓度来体外测定。
由于血容量限制，静脉推注后无法充分采血以定义精确的输入函数，从而无法进行完整的动力学分析。然而，恒速输注需要更少的血样来定义输入函数，从而可以计算分配比，但在 120 分钟后，血浆和组织之间尚未完全达到平衡。
我们的结果表明，血液清除和代谢速度太快，无法在静脉推注后获得可重复的输入函数。平衡分布比不会导致精确的生化参数，但恒速输注更适合，因为组织和血浆之间的分布比在统计学上更精确。恒速输注是研究[(18)F]FP-TZTP 的小动物成像的更好方法。
