[18F]TD-1, a novel GP IIb/IIIa targeted PET tracer for thrombus imaging: design, synthesis, and preclinical imaging evaluation

Thrombotic disease remains a major cause of morbidity and mortality, and rapid noninvasive visualization of active thrombi is still challenging. We designed and synthesized [ 18 F]TD-1, a novel tirofiban-derived positron emission tomography (PET) tracer targeting glycoprotein IIb/IIIa (GP IIb/IIIa) for thrombus imaging, and evaluated its preclinical imaging performance. P-Tiro was synthesized as the radiolabeling precursor, and [ 18 F]TD-1 was prepared via aromatic destannylation followed by quality control. [ 18 F]TD-1 was obtained in 12.1 ± 4.2% non-decay-corrected radiochemical yield, with radiochemical purity ≥ 98% and molar activity > 37 GBq/μmol, and remained stable in vitro for 4 h. Preliminary safety evaluation of TD-1 showed no evident adverse effects during the observation period. In healthy beagle dogs, serial PET/CT imaging suggested predominant hepatobiliary clearance, with additional renal excretion. In a canine pulmonary embolism model, positron emission tomography/computed tomography (PET/CT) visualized thrombi colocalized with embolic sites. Target-to-background contrast peaked at 15 min after injection, suggesting that 15 min may be a practical early time point for static imaging. These findings support further evaluation of [ 18 F]TD-1 as a tirofiban-derived PET tracer for thrombus imaging.