Br J Pharmacol. 2026 Jul 16. doi: 10.1111/bph.70593. Online ahead of print.
ABSTRACT
BACKGROUND AND PURPOSE: Oxidative stress plays a critical role in the pathophysiology of various diseases, yet current methods for its non-invasive detection remain limited. This study aimed to systematically validate a superoxide-selective PET tracer, [18F]FPBT, for the early diagnosis and therapeutic monitoring of oxidative stress-related conditions.
EXPERIMENTAL APPROACH: [18F]FPBT was synthesised using a GMP-compliant, automated production protocol on the Trasis AllinOne platform. The product underwent comprehensive quality control tests to ensure clinical suitability. Preclinical imaging was conducted using a clinical PET scanner in LPS- and doxorubicin-treated rabbits, to assess tracer uptake in organs subject to oxidative stress. Radiation dosimetry was measured in healthy rabbits to estimate effective human doses. Acute toxicity was evaluated using nonradioactive FPBT in KM mice (1.875 mg·kg-1).
KEY RESULTS: [18F]FPBT was successfully produced with batch yields ranging from 2.69 to 4.64 GBq when starting from 19.20-68.45 GBq of fluoride-18. PET imaging demonstrated clear visualisation of cardiac oxidative stress in LPS- and doxorubicin-treated rabbits. Estimated human radiation doses were 0.022 ± 0.004 mSv·MBq-1 for males and 0.028 ± 0.005 mSv·MBq-1 for females, comparable to [18F]FDG. No treatment-related adverse effects were observed in mice administered FBPT at a dose corresponding to 8896-fold the projected nonradioactive mass dose for a 150-MBq [18F]FBPT PET scan in humans.
CONCLUSIONS AND IMPLICATIONS: [18F]FPBT meets the regulatory and biological safety criteria for human use and shows strong potential for first-in-human PET imaging studies. This tracer could enable early diagnosis, monitoring and treatment evaluation in cardiovascular diseases characterised by elevated oxidative stress.
PMID:42463455 | DOI:10.1111/bph.70593