TY - JOUR T1 - Phase I, First-in-Human Study of BMS747158, a Novel <sup>18</sup>F-Labeled Tracer for Myocardial Perfusion PET: Dosimetry, Biodistribution, Safety, and Imaging Characteristics After a Single Injection at Rest JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1490 LP - 1498 DO - 10.2967/jnumed.111.092528 VL - 52 IS - 9 AU - Jamshid Maddahi AU - Johannes Czernin AU - Joel Lazewatsky AU - Sung-Cheng Huang AU - Magnus Dahlbom AU - Heinrich Schelbert AU - Richard Sparks AU - Alexander Ehlgen AU - Paul Crane AU - Qi Zhu AU - Marybeth Devine AU - Michael Phelps Y1 - 2011/09/01 UR - http://jnm.snmjournals.org/content/52/9/1490.abstract N2 - 18F-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 18F 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 18F-labeled BMS747158 appears to be well tolerated and has a unique potential for myocardial perfusion PET. ER -