PT  - JOURNAL ARTICLE
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
TI  - 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
AID  - 10.2967/jnumed.111.092528
DP  - 2011 Sep 01
TA  - Journal of Nuclear Medicine
PG  - 1490--1498
VI  - 52
IP  - 9
4099  - http://jnm.snmjournals.org/content/52/9/1490.short
4100  - http://jnm.snmjournals.org/content/52/9/1490.full
SO  - J Nucl Med2011 Sep 01; 52
AB  - 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.