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

摘要

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.