Glycoprotein IIb/IIIa receptor targeted PET/CT imaging: a novel diagnostic tool for detecting bioprosthetic valve thrombosis. (14th October 2021)

• Record Type: Journal Article
• 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
• Is Part Of: European heart journal. Volume 42(2021)Supplement 1
• Publication Date: 2021-10-14
• Subjects: Valvular Heart Disease; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; 616.12005
• DOI: 10.1093/eurheartj/ehab724.0131
• Languages: English
• ISSNs: 0195-668X

Abstract

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.