PET示踪剂的放射性代谢物会干扰成像,并且在对PET数据进行建模时需要考虑。各种示踪剂和放射性代谢物特性影响进入组织的摄取速率。在这项研究中,我们调查了两个这样的因素,亲脂性和无蛋白质部分。使用薄层色谱和数字放射自显影(radioTLC)和超滤开发了一种新颖的快速方法,用于分析示例性PET示踪剂的无蛋白级分,[11C]SMW139(fP,所有放射性的自由亲本示踪剂),及其放射性代谢物(FM,所有放射性上的游离放射性代谢物)。详细了解放射性代谢物进入血管外细胞的摄取需要分析fM,以前没有对PET示踪剂进行过。用[11C]SMW139注射小鼠,并且分析来自血浆和脑的时间-活性曲线以及亲代部分和游离部分数据,以证明血浆中无蛋白质和蛋白质结合的[11C]SMW139及其放射性代谢物的真实水平。超滤方法包括针对母体示踪剂及其放射性代谢物的单独的膜校正因子,以分析无偏fP和fM。[11C]SMW139代谢迅速,45分钟后,血浆中的亲本分数为0.33,脑中的亲本分数为0.28。超滤膜校正对fP有显着影响,但对fM没有影响。从10-45分钟,fP从0.032下降到0.007,而fM保持在0.52和0.35之间。血浆中更高的fM可以解释为什么亲脂性较低的放射性代谢物有效地进入大脑。啮齿动物对fP和fM的这种详细了解可用于翻译研究中,以解释示踪剂在人类中的行为。类似的亲本部分和血浆蛋白结合方法可用于人体内分析。
Radiometabolites of PET tracers interfere with imaging and need to be taken into account when modeling PET data. Various tracer and radiometabolite characteristics affect the uptake rate into tissue. In this study, we investigated two such factors, lipophilicity and protein-free fraction. A novel rapid method was developed using thin-layer chromatography with digital autoradiography (radioTLC) and ultrafiltration for analyzing the protein-free fractions of an exemplar PET tracer, [11C]SMW139 (fP, free parent tracer over all radioactivity), and its radiometabolites (fM, free radiometabolites over all radioactivity). Detailed understanding of the uptake of radiometabolites into extravascular cells requires analyzing fM, which has not previously been performed for PET tracers. Mice were injected with [11C]SMW139, and time-activity curves from plasma and brain coupled with the parent fraction and free fraction data were analyzed to demonstrate the true levels of protein-free and protein-bound [11C]SMW139 and its radiometabolites in plasma. The ultrafiltration method included separate membrane correction factors for the parent tracer and its radiometabolites for analysis of unbiased fP and fM. Metabolism of [11C]SMW139 was rapid, and after 45 min, the parent fraction was 0.33 in plasma and 0.28 in brain. Ultrafiltration membrane correction had a significant effect on the fP but not the fM. From 10-45 min, the fP decreased from 0.032 to 0.007, while fM remained between 0.52 and 0.35. The much higher fM in plasma could explain why the less lipophilic radiometabolites enter the brain efficiently. This detailed understanding of fP and fM from rodents can be used in translational studies to explain the behavior of the tracer in humans. Similar parent fraction and plasma protein binding methods can be used for human in vivo analysis.