[18F]BIBD-239: A First-in-Human PET Radiotracer with Dual Diagnostic Utility for Glioma Grading and Myocardial Imaging

Abstract

To verify its application potential in the field of cardiac and cerebral disease diagnosis, the first human experiment of [¹⁸F]BIBD-239 was reported. Synthesized via a GMP-compliant automated process on a CFN-MPS200 synthesizer (per Chinese Pharmacopoeia 2020), it achieved radiochemical purity >95%, nondecay-corrected yield >15%, and molar activity >120 GBq/μmol (total synthesis time 80 ± 5 min) under optimized conditions (95 °C, 10 min). Preclinical studies in rats confirmed TSPO-specific binding. First-in-human studies (6 healthy volunteers, 1 high-grade glioma (HGG), 1 low-grade glioma (LGG)) showed it rapidly crossed the blood–brain barrier with low normal brain retention and high sustained myocardial uptake without in vivo defluorination. HGG had higher tumor-to-background ratios (3.09) than LGG (2.33), with uptake beyond MRI-enhanced regions, correlating with histopathology. The whole-body effective dose (0.0145 ± 0.0018 mSv/MBq) was lower than [¹⁸F]FDG. [¹⁸F]BIBD-239 has robust synthesis, favorable pharmacokinetics, and TSPO-specific binding, enabling dual utility in noninvasive glioma grading and glucose-independent myocardial imaging, supporting translation in neuro-oncology and cardiovascular assessment.