Glycoprotein IIb/IIIa receptor targeted PET/CT imaging: a novel diagnostic tool for detecting bioprosthetic valve thrombosis
Authors: Deutsch M A , Zabel R , Preuss R , Lindner O , Friedrichs K , Rudolph T K , Rudolph V , Bleiziffer S , Milting H , Stephens A , Koglin N , Gummert J F , Burchert W , Hugenberg V 
Published: October 2021

Abstract

Background/Introduction
Bioprosthetic valve thrombosis (BPVT) is an important clinical entity eventually following both bioprosthetic surgical and transcatheter aortic valve replacement. Although dynamic contrast-enhanced 4D-MDCT has improved the diagnosis of BPVT, more sensitive and pathology-specific non-invasive imaging tools are lacking. Recently, the glycoprotein IIb/IIIa receptor targeted, elarofiban-derived PET/CT imaging radiotracer [18F]GP1 has been successfully used for visualization of acute venous and arterial thrombi.

Purpose
We hypothesized that [18F]GP1 PET/CT imaging is suitable to detect BPVT.

Methods
In this proof-of-concept study, patients after bioprosthetic aortic valve replacement with symptomatic, severe hemodynamic valve dysfunction and confirmed hypoattenuated leaflet thickening (HALT) in dynamic 4D-MDCT were offered to participate in compassionate use examinations to undergo PET/CT imaging with the investigational [18F]GP1 PET tracer at baseline and after a 12-week course of therapeutic oral anticoagulation.

Results
This case series reports on three patients after aortic valve replacement. Two patients with symptomatic, obstructive BPVT as confirmed by echocardiography and 4D-MDCT fulfilled specified criteria and underwent [18F]GP1 PET/CT imaging. [18F]GP1 PET/CT clearly distinguished between blood pool activity and thrombotic foci. Clot-to-blood ratios at baseline were 8.2 and 4.5, respectively. A 12-week trial of therapeutic oral anticoagulation was associated with a regression of mean transprosthetic pressure gradient and reversal of HALT. Follow-up 4D-MDCT corroborated thrombus resolution in both patients. Correspondingly, [18F]GP1 PET/CT imaging demonstrated decreased tracer uptake in both patients. Clot-to-blood ratio at follow-up visit decreased to 1.2 and 2.9, respectively. While absent tracer uptake was seen in patient #1, residual tracer uptake was observed in patient #2 suggestive of ongoing platelet aggregation. One asymptomatic SAVR patient was examined with [18F]GP1 PET/CT for a different compassionate use and no thrombotic foci were detected on the leaflets.

Conclusions
[18F]GP1 PET/CT is a novel imaging technique in patients with obstructive BPVT. In a head-to-head comparison we show that [18F]GP1 PET/CT may have incremental diagnostic value over dynamic contrast-enhanced 4D-MDCT alone by detection of sites of ongoing platelet aggregation at the molecular level. [18F]GP1 PET/CT may serve as a novel, highly sensitive tool to overcome some limitations of current diagnostic imaging modalities for detecting BPVT and may prove useful for the monitoring and guidance of therapeutic interventions.

Funding Acknowledgement
Type of funding sources: Other. Main funding source(s): Life Molecular Imaging provided material for [18F]GP1 radiolabeling free of charge as part of an ongoing research collaboration.