Imaging, Merck Research Laboratories, Sumneytown Pike WP44D-2, West Point, PA 19486, USA.
Eur J Nucl Med Mol Imaging. 2010 May;37(5):920-33. doi: 10.1007/s00259-009-1340-5. Epub 2009 Dec 24.
Quantitative imaging of the type 1 cannabinoid receptor (CB1R) opens perspectives for many neurological and psychiatric disorders. We characterized the kinetics and reproducibility of the CB1R tracer [(18)F]MK-9470 in human brain.
[(18)F]MK-9470 data were analysed using reversible models and the distribution volume V (T) and V (ND) k (3) (V (ND) k (3) = K (1) k (2)) were estimated. Tracer binding was also evaluated using irreversible kinetics and the irreversible uptake constant K (i) and fractional uptake rate (FUR) were estimated. The effect of blood flow on these parameters was evaluated. Additionally, the possibility of determining the tracer plasma kinetics using a reduced number of blood samples was also examined.
A reversible two-tissue compartment model using a global k (4) value was necessary to describe brain kinetics. Both V (T) and V (ND) k (3) were estimated satisfactorily and their test-retest variability was between 10% and 30%. Irreversible methods adequately described brain kinetics and FUR values were equivalent to K (i). The linear relationship between K (i) and V (ND) k (3) demonstrated that K (i) or FUR and thus the simple measure of tracer brain uptake provide CB1R availability information. The test-retest variability of K (i) and FUR was <10% and estimates were independent of blood flow. Brain uptake can be used as a receptor availability index, albeit at the expense of potential bias due to between-subject differences in tracer plasma kinetics.
[(18)F]MK-9470 specific binding can be accurately determined using FUR values requiring a short scan 90 to 120 min after tracer administration. Our results suggest that [(18)F]MK-9470 plasma kinetics can be assessed using a few venous samples.
1 型大麻素受体（CB1R）的定量成像为许多神经和精神疾病开辟了新的前景。我们对人体大脑中 CB1R 示踪剂 [(18)F]MK-9470 的动力学和可重复性进行了特征描述。
使用可逆模型分析 [(18)F]MK-9470 数据，并估计分布容积 V（T）和 V（ND）k（3）（V（ND）k（3）=K（1）k（2））。还使用不可逆动力学评估示踪剂结合，估计不可逆摄取常数 K（i）和分数摄取率（FUR）。评估了血流对这些参数的影响。此外，还研究了使用较少数量的血样来确定示踪剂血浆动力学的可能性。
使用全局 k（4）值的可逆两室模型来描述脑动力学是必要的。V（T）和 V（ND）k（3）均能得到满意的估计，其测试-重测变异性在 10%至 30%之间。不可逆方法能很好地描述脑动力学，且 FUR 值与 K（i）相当。K（i）与 V（ND）k（3）之间的线性关系表明，K（i）或 FUR，以及示踪剂脑摄取的简单测量值，提供了 CB1R 可利用性信息。K（i）和 FUR 的测试-重测变异性<10%，且估计值与血流无关。脑摄取可用作受体可用性指数，尽管这是以由于示踪剂血浆动力学的个体间差异而产生潜在偏差为代价的。
使用 FUR 值可以准确确定 [(18)F]MK-9470 的特异性结合，需要在示踪剂给药后 90 至 120 分钟进行短扫描。我们的结果表明，可以使用少量静脉样本评估 [(18)F]MK-9470 的血浆动力学。
