Department of Molecular and Medical Pharmacology Nuclear Medicine, David Geffen School of Medicine at University of California, Los Angeles, California 90095-7064, USA.
J Nucl Med. 2011 Sep;52(9):1490-8. doi: 10.2967/jnumed.111.092528. Epub 2011 Aug 17.
(18)F-labeled BMS747158 is a novel myocardial perfusion imaging tracer that targets mitochondrial complex 1. The objectives of this phase I study were to evaluate radiation dosimetry, biodistribution, human safety, tolerability, and early elimination of (18)F activity in urine after injection of a single dose of the tracer at rest in healthy subjects.
Thirteen healthy subjects were injected with 170-244 MBq (4.6-6.6 mCi) of BMS747158 intravenously. Dynamic PET was obtained over the heart for 10 min, followed by sequential whole-body imaging for 5 h. Blood samples and urinary excretion were collected for up to 8 h. Heart rate, electrocardiogram, and blood pressure were monitored before and during imaging. The residence times were determined from multiexponential regression of organ region-of-interest data normalized by injected dose. Absorbed dose estimates for all target organs were determined using MIRD schema with OLINDA/EXM software.
The organ receiving the largest mean absorbed dose was the kidneys at 0.066 mSv/MBq (0.24 rem/mCi), followed by the heart wall at 0.048 mSv/MBq (0.18 rem/mCi). The mean effective dose was 0.019 mSv/MBq (0.072 rem/mCi). The heart exhibited high and sustained retention of BMS747158 from the earliest images through approximately 5 h after injection. There were no drug-related adverse events, and the tracer was well tolerated in all subjects. Mean urinary excretion was 4.83 percentage injected dose (range, 0.64-12.41 percentage injected dose).
These preliminary data suggest that (18)F-labeled BMS747158 appears to be well tolerated and has a unique potential for myocardial perfusion PET.
评估放射性剂量、生物分布、人体安全性、耐受性以及在健康受试者中单次静注示踪剂后尿液中（18）F 活性的早期消除情况。
13 名健康受试者静脉注射 170-244MBq（4.6-6.6mCi）的 BMS747158。注射后 10min 内进行心脏动态 PET 扫描，随后进行 5h 的全身连续成像。在 8h 内采集血样和尿液。在成像前和成像期间监测心率、心电图和血压。通过对归一化为注射剂量的器官感兴趣区数据进行多指数回归来确定停留时间。使用 MIRD 方案和 OLINDA/EXM 软件确定所有靶器官的吸收剂量估计值。
肾脏是吸收剂量最大的器官，平均吸收剂量为 0.066mSv/MBq（0.24 毫希/毫居里），其次是心肌壁，平均吸收剂量为 0.048mSv/MBq（0.18 毫希/毫居里）。平均有效剂量为 0.019mSv/MBq（0.072 毫希/毫居里）。心脏在注射后最早的图像中一直保持高且持续的 BMS747158 保留，直至约 5h 后。所有受试者均未发生与药物相关的不良事件，且示踪剂均耐受良好。平均尿液排泄率为 4.83%注射剂量（范围：0.64-12.41%注射剂量）。
这些初步数据表明，（18）F 标记的 BMS747158 似乎具有良好的耐受性，并且具有独特的心肌灌注 PET 潜力。
