Department of Radiology, Division of Nuclear Medicine, University of Michigan Medical School, Ann Arbor, Michigan.
J Nucl Med. 2014 Mar;55(3):396-404. doi: 10.2967/jnumed.113.124792. Epub 2014 Jan 30.
(-)-5-(18)F-fluoroethoxybenzovesamicol ((18)F-FEOBV) is a vesamicol derivative that binds selectively to the vesicular acetylcholine transporter (VAChT) and has been used in preclinical studies to quantify presynaptic cholinergic nerve terminals. This study presents, to our knowledge, the first-in-human experience with (18)F-FEOBV, including radiation dosimetry, biodistribution, tolerability and safety in human subjects, and brain kinetics and methods for quantitative analysis of (18)F-FEOBV.
Whole-body (18)F-FEOBV scans were obtained in 3 healthy human volunteers. Seven additional subjects underwent dynamic brain imaging 0-120, 150-180, and 210-240 min after bolus injection of (18)F-FEOBV. Arterial blood sampling was performed with chromatographic identification of authentic (18)F-FEOBV to determine the arterial plasma input function. Analysis methods included nonlinear least-squares fitting of a 2-tissue-compartmental model, reference tissue modeling, and late single-scan imaging.
No pharmacologic or physiologic changes were observed after intravenous administration of up to 1.3 μg of (18)F-FEOBV. Radiation dosimetry estimates indicate that more than 400 MBq may be administered without exceeding regulatory radiation dose limits. Kinetic analysis showed brain uptake to be relatively high with single-pass extraction of 25%-35%. VAChT binding estimates varied by a factor of greater than 30 between the striatum and cortex. Coefficients of variation in k3 estimates varied from 15% to 30%. Volume of distribution measures yielded a dynamic range of approximately 15 but with little reduction in variability. Reference tissue approaches yielded more stable estimates of the distribution volume ratio (1 + BPND), with coefficients of variation ranging from 20% in the striatum to 6%-12% in cortical regions. The late static distribution of (18)F-FEOBV correlated highly with the distribution volume ratio estimates from reference tissue models (r = 0.993).
(18)F-FEOBV PET confirms that the tracer binds to VAChT with the expected in vivo human brain distribution. Both reference tissue modeling and late static scanning approaches provide a robust index of VAChT binding.
介绍（-）-5-（18）F-氟乙氧基苯并戊醇（（18）F-FEOBV）在人体中的初步经验，包括辐射剂量学、生物分布、人体耐受性和安全性，以及（18）F-FEOBV 的脑内动力学和定量分析方法。
3 名健康志愿者进行了全身（18）F-FEOBV 扫描。另外 7 名受试者在静脉注射（18）F-FEOBV 后 0-120、150-180 和 210-240 分钟进行了动态脑成像。通过色谱法鉴定真实的（18）F-FEOBV 进行动脉血样采集，以确定动脉血浆输入函数。分析方法包括 2 组织室模型的非线性最小二乘法拟合、参考组织建模和晚期单扫描成像。
静脉注射高达 1.3 μg 的（18）F-FEOBV 后，未观察到任何药理或生理变化。辐射剂量学估算表明，超过 400 MBq 的剂量可能不会超过监管辐射剂量限制。动力学分析显示，脑摄取相对较高，单通过提取 25%-35%。纹状体和皮质之间的 VAChT 结合估计值差异大于 30 倍。k3 估计值的变异系数在 15%-30%之间变化。分布容积测量值产生约 15 的动态范围，但变异性减小。参考组织方法产生了分布容积比（1+BPND）更稳定的估计值，纹状体的变异系数范围为 20%，皮质区域为 6%-12%。晚期（18）F-FEOBV 的静态分布与参考组织模型的分布容积比估计值高度相关（r=0.993）。
（18）F-FEOBV PET 证实，示踪剂与 VAChT 结合，具有预期的人类大脑分布。参考组织模型和晚期静态扫描方法均可提供 VAChT 结合的可靠指标。
