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

Sun Young Chae; Tae-Won Kwon; Soyoung Jin; Sun U Kwon; Changhwan Sung; Seung Jun Oh; Sang Ju Lee; Jungsu S Oh; Youngjin Han; Yong-Pil Cho; Narae Lee; Ji Young Kim; Norman Koglin; Mathias Berndt; Andrew W Stephens; Dae Hyuk Moon

doi:10.1186/s13550-018-0471-8

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

EJNMMI Res. 2019 Jan 7;9(1):3. doi: 10.1186/s13550-018-0471-8.

Authors

Affiliations

¹ Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.
² Department of Vascular Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
³ Department of Nuclear Medicine, Nowon Eulji Medical Center, Eulji University, Seoul, Republic of Korea.
⁴ Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
⁵ Department of Nuclear Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
⁶ Department of Nuclear Medicine, Guri Hospital of Hanyang University Medical Center, Hanyang University College of Medicine, Seoul, Republic of Korea.
⁷ Life Molecular Imaging GmbH (formerly Piramal Imaging GmbH), Berlin, Germany.
⁸ Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea. [email protected].

Abstract

Background: ¹⁸F-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.

Methods: Adult 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.

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). 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.

Conclusions: ¹⁸F-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.

Keywords: 18F-GP1; Arterial thrombosis; Glycoprotein IIb/IIIa receptor; Platelet activation; Positron emission tomography.

Associated data

ClinicalTrials.gov/NCT02864810