Exploratory clinical trial of [^sup 18^F]GP1 for imaging arterial or venous thromboembolism using positron emission tomography: interim analysis of an open-label, single center study

Objectives: [18F]GP1 is a new positron emission tomography (PET) tracer that targets glycoprotein IIb/IIIa (GPIIb/IIIa) receptors on activated platelets. The aim of this study was to explore the detection rate of thromboembolic foci with [18F]GP1 PET. The safety, metabolism, pharmacokinetics and biodistribution of [18F]GP1 were also investigated. Methods: Patients with deep vein thrombosis (DVT, n=4), pulmonary embolism (PE, n=5) or arterial thromboembolism (ATE, n=6: one cerebral infarction, and five subjects after endovascular abdominal aortic aneurysm repair) who had acute thromboembolic focus/foci confirmed by standard imaging modalities were enrolled and included in this analysis. Dynamic whole-body PET images with [18F]GP1 were acquired for up to 140 min after injection of approximately 250 MBq of [18F]GP1. Plasma samples were obtained for metabolite analysis. For lesion based analysis, the investigator selected up to five of the largest lesions on standard images as reference. Reference lesions were defined for each external iliac, femoral, popliteal, tibial and peroneal vein for DVT; pulmonary trunk, main and lobar pulmonary artery (segmental pulmonary arteries included in each lobar pulmonary artery) for PE; and abdominal aorta and systemic artery for ATE. Results: [18F]GP1 administration and PET procedures were well tolerated in all patients. One patient had clinically relevant changes in safety parameters but those were assessed as not study drug-related adverse events. No plasma metabolites were detected in 14/15 (93%) subjects. [18F]GP1 PET showed initial uptake in the spleen, kidney, liver, and blood pool with rapid clearance. The overall image quality was adequate for diagnosis in all patients. [18F]GP1 PET identified thromboembolic foci in all 15 patients. Lesion based analysis revealed that [18F]GP1 PET detected 18 of 18 (100%) lesions in DVT, 18 of 24 (75%) lesions in PE, and 6 of 7 (86%) lesions in ATE. The maximum standardized uptake value (SUV) of thromboembolic foci and the ratio of SUV in a lesion and the SUV of a reference tissue (SUVR) were 5.89 ± 2.71 and 4.97 ± 1.85 for DVT, 4.99±2.35 and 4.24±2.01 for PE and 5.07±1.95 and 5.34±2.17 for ATE, respectively. Additional thromboembolic lesions were identified by [18F]GP1 PET in 7 of 15 (47%) patients (2 DVT, 4 PE and 1 ATE), which led to further diagnostic studies. Those lesions included 22 DVT (2 proximal and 20 distal), 25 PE (10 lobar, 1segmental and 14 subsegmental arteries), 1 ri