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

Abstract

Tennessee18 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. 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 regionof-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 drugrelated 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 18 F-labeled BMS747158 appears to be well tolerated and has a unique potential for myocardial perfusion PET.

Pet Imaging and its Application in Cardiovascular Diseases

“…Flurpiridaz F-18 can detect milder perfusion defects with better accuracy, reflecting the true extent of perfusion defects compared to SPECT probes such as the 99m Tc-labelled tracers. 32 The results in phase 2 studies also proved that flurpiridaz F-18 PET imaging has higher sensitivity than SPECT. 33 The phase 3 study to further confirm these results is currently ongoing.…”

Achieving Very-Low-Dose Radiation Exposure in Cardiac Computed Tomography, Single-Photon Emission Computed Tomography, and Positron Emission Tomography

“…For the newly introduced fluorine-18 labeled radiotracer 18 F flurpiridaz, a mean effective combined rest-stress dose has been reported to be 5 to 6 mSv in phase I and II trials. 80,81 It is to be noted that pharmacological PET imaging offers true stress (rather than poststress) functional measurements and allows time-efficient (<30 minutes) stress-rest protocols. 78 Analogous to stress-only SPECT MPI imaging, it is also possible to perform stress-only low-dose PET imaging.…”

Advances in clinical application of quantitative myocardial perfusion imaging

“…Moreover, the generator produced flow tracer 82 Rubidium ( 82 Rb) has made perfusion imaging possible at sites without onsite cyclotron. Still, 13 N-labeled ammonia ( 13 NH 3 ) and 15 O-labeled water (H 2 15 O) are the most often used validated PET tracers for quantification of regional myocardial perfusion. However, they have short half-lives (10 and 2 minutes, respectively) and so they both require on-site cyclotron, which limits their widespread clinical use.…”