Biodistribution of [¹⁸F]BCPP-BF in humans: a first-in-human positron emission tomography study

[¹⁸F]BCPP-BF and [¹⁸F]BCPP-EF are PET probes used to evaluate mitochondrial function by targeting MC-I. Clinical studies on [¹⁸F]BCPP-EF have been reported, particularly brain studies. However, no reports exist on the use of [¹⁸F]BCPP-BF in humans. Therefore, in this study, we aimed to apply [¹⁸F]BCPP-BF to humans for the first time to assess its safety and radiation dose. We also aimed to explore the whole-body distribution of both probes by comparing the data acquired from the same participants.

Ten healthy participants underwent whole-body PET/CT measurements of [¹⁸F]BCPP-BF (117.0-153.8 MBq/body) for 90 min. Approximately 2-3 weeks after the measurements, the participants underwent [¹⁸F]BCPP-EF (109.2-158.8 MBq/body) measurements. Thirteen volumes of interest (VOIs) were manually drawn on the brain and peripheral organs using PET/CT images to evaluate the distribution and kinetics of the probes. The equivalent dose for each organ and the whole-body effective dose for each participant were calculated according to the Medical Internal Radiation Dose schema using OLINDA/EXM software.

The highest radiation doses from the administration of [¹⁸F]BCPP-BF were observed in the small intestine (65.5 ± 8.7 μGy/MBq), and the estimated effective dose (16.3 ± 2.3 μSv/MBq) was well-tolerated. There were no clinically significant safety concerns. A high accumulation of [¹⁸F]BCPP-BF was observed in the kidney, pancreas, and heart, consistent with the findings in previously reported animal studies. The distributions of both tracers were similar. However, the kinetics of [¹⁸F]BCPP-BF were different, with higher uptake and slower washout in the kidney and pancreas, and lower uptake and slower washout in the brain and liver, from those of [¹⁸F]BCPP-EF.

[¹⁸F]BCPP-BF is safe and acceptable for clinical use owing to its low toxicity and radiation dose. [¹⁸F]BCPP-BF and [¹⁸F]BCPP-EF generally exhibited similar whole-body distributions; however, their organ-specific kinetics differed slightly. The appropriate selection of these probes can provide a more accurate assessment of human mitochondrial function.