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

Abstract

Background18F-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 18F-GP1 PET/computed tomography (PET/CT) and to quantitatively assess 18F-GP1 uptake. Safety, biodistribution, pharmacokinetics and metabolism were also evaluated.MethodsAdult patients who had signs or symptoms of AAT or had recently undergone arterial intervention or surgery within 14 days prior to 18F-GP1 PET/CT were eligible for inclusion. The AAT focus was demonstrated by conventional imaging within the 5 days prior to 18F-GP1 administration. Whole-body dynamic 18F-GP1 PET/CT images were acquired for up to 140 min after injection of 250 MBq of 18F-GP1. Venous plasma samples were analysed to determine 18F-GP1 clearance and metabolite formation.ResultsAmong 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). 18F-GP1 administration and PET/CT procedures were well tolerated, with no drug-related adverse events. All patients showed high initial 18F-GP1 uptake in the spleen, kidney and blood pool, followed by rapid clearance. Unmetabolised plasma 18F-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 18F-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.Conclusions18F-GP1 is a safe and promising novel PET tracer for imaging AAT with a favourable biodistribution and pharmacokinetic profile.Trial registrationClinicalTrials.gov identifier: NCT02864810, Registered August 3, 2016.Electronic supplementary materialThe online version of this article (10.1186/s13550-018-0471-8) contains supplementary material, which is available to authorized users.

Detection and Characterization of Thrombosis in Humans using Fibrin-Targeted Positron Emission Tomography and Magnetic Resonance

“…99m Tc-apcitide was also shown to be ineffectual for diagnosis of PE ( 5 ). More recently, a PET probe targeting the GP2B3A receptor has been used to successfully image acute arterial and venous thrombi ( 4, 6 ). However, the specificity of this agent remains unknown, and the targeting of activated platelets, through the GP2B3A receptor, supports the detection only of active, hyperacute platelet-rich thrombi.…”

“…In the case of thrombosis this would include thrombus age, platelet content, fibrin content, risk of embolism and potential for lysis. A number of molecular imaging approaches incorporating different imaging modalities and targeting platelets ( 4–10 ), fibrin ( 11–16 ), d-dimers ( 17–20 ), or fibrinogen ( 21 ), have been proposed over the years, with some progressing to clinical trials ( 3, 22 ). However these agents have been limited by suboptimal pharmacokinetics, high blood background, low specificity, or sensitivity only to hyperacute/acute thrombi( 3 ).…”

Platelets in Multiple Sclerosis: Early and Central Mediators of Inflammation and Neurodegeneration and Attractive Targets for Molecular Imaging and Site-Directed Therapy

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“…Clinical work has highlighted the development of the PET tracer 18 F-GP1, which is a novel tracer with a high affinity for GPIIb/IIIa on platelet surfaces (102). Following 18 F-GP1 injection, PET/CT researchers were able to monitor this tracer in a dynamic and systemwide manner, while analyzing plasma samples to assess 18 F-GP1 clearance and metabolism (103). They found that 18 F-GP1 exhibited satisfactory biodistribution and pharmacokinetic properties that made it ideal for the detection of atherosclerotic thrombosis.…”