Phase I, First-in-Human Study of BMS747158, a Novel 18F-Labeled Tracer for Myocardial Perfusion PET: Dosimetry, Biodistribution, Safety, and Imaging Characteristics After a Single Injection at Rest
Phase I, First-in-Human Study of BMS747158, a Novel 18F-Labeled Tracer for Myocardial Perfusion PET: Dosimetry, Biodistribution, Safety, and Imaging Characteristics After a Single Injection at Rest
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DOI：
10.2967/jnumed.111.092528
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发表时间：
2011-09-01
影响因子：
9.3
通讯作者：
Phelps, Michael
中科院分区：
文献类型：
--
作者：
Maddahi, Jamshid;Czernin, Johannes;Phelps, Michael
F-18标记的BMS747158是一种新的以线粒体复合体1为靶点的心肌灌注成像示踪剂。这项I期研究的目标是评估健康受试者注射单剂量示踪剂后的辐射剂量、生物分布、人体安全性、耐受性和尿中F-18活性的早期消除。方法：13名健康受试者静脉注射BMS747158 170~244MBq(4.6~6.6MCI)。动态心肌显像10min，连续全身显像5h，采集血样和尿液8h，监测显像前、中心率、心电图和血压。停留时间由注射剂量归一化的器官感兴趣区数据的多指数回归确定。所有靶器官的吸收剂量估计值使用Olinda/exm软件的MIRD方案确定。结果：平均吸收剂量最大的器官是肾脏，平均吸收剂量为0.066 mSv/mBq(0.24rem/mCi)，其次是心壁，平均吸收剂量为0.048 mSv/mBq(0.18rem/mci)。平均有效剂量为0.019 mSv/mBq(0.072 rem/mCi)。心脏表现出从最早的图像到注射后大约5小时BMS747158的高度和持续的滞留。没有与药物有关的不良反应，示踪剂在所有受试者中耐受性良好。平均尿排泄量为4.83%注射剂量(0.64%~12.41%注射剂量)。结论：这些初步数据表明，F-18标记的BMS747158似乎具有良好的耐受性，并具有独特的心肌灌注PET潜力。
F-18-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, bio-distribution, human safety, tolerability, and early elimination of F-18 activity in urine after injection of a single dose of the tracer at rest in healthy subjects. Methods: 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. Results: 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). Conclusion: These preliminary data suggest that F-18-labeled BMS747158 appears to be well tolerated and has a unique potential for myocardial perfusion PET.