Detailed pharmacokinetic features of a novel bis-boron 18F-trifluoroborate acid in healthy volunteers: comparable and additional values of total-body PET-imaging-derived analysis.

Purpose To characterize the systemic and organ-specific pharmacokinetics (PK) of a novel bis-boron tracer, [18F]BBPA, using total-body PET imaging in comparison with conventional blood sampling.Methods Ten healthy volunteers underwent 60-minute dynamic total-body [18F]BBPA PET, followed by three static scans (up to 240 min p.i.), alongside 11 venous blood sampling. Regions of interest were drawn on PET in their right atrium, superior vena cava (SVC), and inferior vena cava (IVC) to obtain image-derived blood time-activity curves (TACs), as well as in major organs to obtain tissue TACs. PK parameters of [18F]BBPA were assessed using both blood samples and image-derived blood TACs. Additionally, tissue TACs were analyzed for organ-specific PK and fitted with an tissue-compartment models for kinetic rates of [18F]BBPA.Results [18F]BBPA exhibited rapid clearance (6.58 ± 0.57 L/h, a short elimination half-life (186.48 ± 30.29 min), and a volume of distribution of 29.22 ± 3.52 L. Image-derived PK results were comparable to those obtained from blood sampling, with the relative differences < 13% for SVC and < 15% for IVC. Imaging-derived method captured higher Cmax and shorter Tmax, primarily due to its superior temporal resolution. Organ-specified PK revealed low tissue affinity (partition coefficient < 1.0 in most organs) and minimal metabolic trapping (k3 < 0.06 min- 1 and k2 > K1 in the majority of organs).Conclusion [18F]BBPA exhibits favorable PK properties, including rapid distribution, low normal-tissue affinity, and quick clearance. Total-body PET-image-derived method provides a reliable, non-invasive alternative to conventional blood sampling while offering additional, detailed organ-level kinetic insights.Clinical Trial Registration This is a phase I clinical trial approved by the National Medical Products Administration of China and was registered at www.chinadrugtrials.org.cn (CTR20233997).