A phase 1, first-in-human study of (18)F-GP1 positron emission tomography for imaging acute arterial thrombosis

BACKGROUND: (18)F-GP1 is a novel positron emission tomography (PET) tracer that targets glycoprotein IIb/IIIa receptors on activated platelets. The study objective was to explore the feasibility of directly imaging acute arterial thrombosis (AAT) with (18)F-GP1 PET/computed tomography (PET/CT) and to quantitatively assess (18)F-GP1 uptake. Safety, biodistribution, pharmacokinetics and metabolism were also evaluated. METHODS: Adult patients who had signs or symptoms of AAT or had recently undergone arterial intervention or surgery within 14 days prior to (18)F-GP1 PET/CT were eligible for inclusion. The AAT focus was demonstrated by conventional imaging within the 5 days prior to (18)F-GP1 administration. Whole-body dynamic (18)F-GP1 PET/CT images were acquired for up to 140 min after injection of 250 MBq of (18)F-GP1. Venous plasma samples were analysed to determine (18)F-GP1 clearance and metabolite formation. RESULTS: Among the ten eligible patients assessed, underlying diseases were abdominal aortic aneurysm with endovascular repair (n = 6), bypass surgery and stent placement (n = 1), endarterectomy (n = 1), arterial dissection (n = 1) and acute cerebral infarction (n = 1). (18)F-GP1 administration and PET/CT procedures were well tolerated, with no drug-related adverse events. All patients showed high initial (18)F-GP1 uptake in the spleen, kidney and blood pool, followed by rapid clearance. Unmetabolised plasma (18)F-GP1 levels peaked at 4 min post-injection and decreased over time until 120 min. The overall image quality was sufficient for diagnosis in all patients and AAT foci were detected in all participants. The (18)F-GP1 uptake in AAT foci remained constant from 7 min after injection and began to separate from the blood pool after 20 min. The median standardised uptake value of AAT was 5.0 (range 2.4–7.9) at 120 min post-injection. The median ratio of standardised uptake value of AAT foci to the mean blood pool activity was 3.4 (range 2.0–6.3) at 120 min. CONCLUSIONS: (18)F-GP1 is a safe and promising novel PET tracer for imaging AAT with a favourable biodistribution and pharmacokinetic profile. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02864810, Registered August 3, 2016. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13550-018-0471-8) contains supplementary material, which is available to authorized users.