Glycoprotein IIb/IIIa receptor imaging with ¹⁸F-GP1 positron emission tomography for acute venous thromboembolism: an open-label, non-randomized, first-in-human phase 1 study

¹⁸F-GP1 is a derivative of elarofiban with a high affinity to activated platelet glycoprotein IIb/IIIa (GPIIb/IIIa) and favorable in vivo characteristics for thrombus imaging in preclinical models. We aimed to explore the detection rate of thromboembolic foci with ¹⁸F-GP1 positron emission tomography/computed tomography (PET/CT) in patients with acute venous thromboembolism (VTE), and to evaluate the safety, biodistribution, pharmacokinetics, and metabolism of ¹⁸F-GP1. Methods: We studied patients who had signs or symptoms of acute deep vein thrombosis (DVT) of the leg or acute pulmonary embolism (PE) within 14 days prior to ¹⁸F-GP1 PET/CT, and had thromboembolic foci confirmed by conventional imaging (n = 10 for DVT and n = 10 for PE). Dynamic whole-body PET/CT images were acquired for up to 140 minutes after injection of 250 MBq of ¹⁸F-GP1. Results:¹⁸F-GP1 PET/CT was well tolerated without any drug-related adverse events, and showed high initial uptake in spleen, kidney, and blood pool, followed by rapid clearance. The overall image quality was excellent and allowed interpretation in all patients. ¹⁸F-GP1 PET/CT identified thromboembolic foci in all 20 patients with either DVT or PE. Vessel-level analysis revealed that ¹⁸F-GP1 PET/CT detected 89% (68/76) of vessels with DVT, and 60% (146/245) for PE. Importantly, ¹⁸F-GP1 PET/CT showed increased uptake in 32 vessels that were not detected by conventional imaging, of which 25 were located in distal veins of the lower extremity in 12 patients. A positive correlation was found between ¹⁸F-GP1 uptake and P-selectin-positive circulating platelets (r = 0.656, P = 0.002). Conclusion:¹⁸F-GP1 is a promising PET tracer for imaging acute VTE in patients. ¹⁸F-GP1 PET/CT may identify thrombi in distal veins of the leg, where conventional imaging has limitations.