Glycoprotein IIb/IIIa Receptor Imaging with F-18-GP1 PET for Acute Venous Thromboembolism: An Open-Label, Nonrandomized, Phase 1 Study

Abstract

F-18-GP1 is a derivative of elarofiban with a high affinity to activated platelet glycoprotein IIb/IIIa and favorable in vivo characteristics for thrombus imaging in preclinical models. We aimed to explore the detection rate of thromboembolic foci with F-18-GP1 PET/CT in patients with acute venous thromboembolism and to evaluate the safety, biodistribution, pharmacokinetics, and metabolism of F-18-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 d before F-18-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 min after injection of 250 MBq of F-18-GP1. Results: F-18-GP1 PET/CT was well tolerated, without any drug-related adverse events, and showed high initial uptake in the spleen, kidneys, and blood pool, followed by rapid clearance. The overall image quality was excellent and allowed interpretation in all patients. F-18-GP1 PET/CT identified thromboembolic foci in all 20 patients with either DVT or PE. Vessel-level analysis revealed that F-18-GP1 PET/CT detected 89% (68/76) of vessels with DVT and 60% (146/245) with PE. Importantly, F-18-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 F-18-GP1 uptake and P-selectin-positive circulating platelets (r = 0.656, P=0.002). Conclusion: F-18-GP1 is a promising PET tracer for imaging acute venous thromboembolism in patients. F-18-GP1 PET/CT may identify thrombi in distal veins of the leg, where conventional imaging has limitations.