A Prospective Diagnostic Trial of Al[¹⁸F]F-NOTA-folate PET in Patients With Suspected Cardiac Sarcoidosis and Infective Endocarditis

Turku University Hospital143 enrolled

Overview

The goal of this prospective diagnostic study is to evaluate the imaging characteristics, diagnostic performance, radiation dosimetry, and safety of Al\[¹⁸F\]F-NOTA-folate PET imaging in patients with suspected cardiac sarcoidosis and infective endocarditis, and healthy volunteers. The study is non-interventional with respect to clinical management, and all diagnostic and therapeutic decisions are made according to routine clinical practice independent of study participation. The main aims are to evaluate quantitative uptake of Al\[¹⁸F\]F-NOTA-folate measured by PET imaging in the left ventricular myocardium of patients with suspected cardiac sarcoidosis, and in cardiac valves or prosthetic valve regions in patients with suspected infective endocarditis. Participants will undergo PET imaging with Al\[¹⁸F\]F-NOTA-folate tracer at the Turku PET Centre. Participants with suspected cardiac sarcoidosis will undergo a second PET imaging study after initiation of immunosuppressive therapy.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Enrollment

143

Conditions

Cardiac Sarcoidosis Infective Endocarditis

Al[¹⁸F]F-NOTA-folate PET imagingDIAGNOSTIC_TEST

Imaging is performed in all study groups to assess myocardial, valvular, and extracardiac tracer uptake using a total-body PET/CT system (Siemens Quadra, Siemens Healthcare, Erlangen, Germany). Imaging will cover the region from head to mid-thighs to enable assessment of both cardiac and extracardiac tracer uptake. Serum and plasma samples, ECG and vital signs are collected during the imaging study visit.

[15O]water PET imagingDIAGNOSTIC_TEST

Resting myocardial perfusion imaging using \[15O\]water PET is performed only in patients with suspected cardiac sarcoidosis to assess myocardial perfusion and support interpretation of Al\[18F\]F-NOTA-folate uptake.

EchocardiographyDIAGNOSTIC_TEST

Transthoracic echocardiography (GE Vivid 95, GE Healthcare, Hjorten, Norway) will be performed in patients with suspected cardiac sarcoidosis to assess left ventricular structure and function. Acquisition and analysis will follow standard clinical protocols. Echocardiography will be performed during the same visits as PET imaging.

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Ability to provide written informed consent * Suspected cardiac sarcoidosis group: clinical suspicion of cardiac sarcoidosis requiring diagnostic evaluation, including cardiac magnetic resonance and/or \[¹⁸F\]FDG PET * Suspected infective endocarditis group: clinical suspicion of native or prosthetic valve infective endocarditis requiring diagnostic evaluation * Healthy volunteers group: * Age above 50 and post-menopausal (women) * No history of cardiovascular disease, systemic inflammatory disease, malignancy, and no active infection Exclusion Criteria: * Pregnancy or breastfeeding * Known hypersensitivity to folate-based compounds or investigational medical product excipients * Unwillingness or inability to use effective contraception during the study participation period, in participants of childbearing potential * Severe renal impairment (CKD-EPI GFR \<20ml/min) * Clinically unstable condition that, in the opinion of the investigator, would make study imaging unsafe or not feasible (e.g., haemodynamic instability, decompensated heart failure, uncontrolled clinically significant arrhythmia, suspicion of acute coronary syndrome) * Systemic immunosuppressive therapy for more than 7 days prior to baseline Al\[18F\]F-NOTA-folate PET imaging * Inability to complete protocol-defined study procedures * Women of childbearing potential must have a negative pregnancy test prior to tracer administration

Outcomes

Primary Outcomes

Quantitative uptake of Al[¹⁸F]F-NOTA-folate measured by PET in the left ventricular myocardium in patients with suspected cardiac sarcoidosis.

Quantitative uptake of Al\[¹⁸F\]F-NOTA-folate on PET in the left ventricular myocardium (global and regional standardized uptake value (SUV) measures derived from polar map analysis) in suspected cardiac sarcoidosis.

Time frame: Visit 2 (baseline imaging), no later than 7 days after initiation of systemic immunosuppressive therapy.

Quantitative uptake of Al[¹⁸F]F-NOTA-folate measured by PET in infected versus non-infected cardiac valves or prostheses in patients with suspected infective endocarditis

Quantitative uptake of Al\[¹⁸F\]F-NOTA-folate on PET in the valve/prosthesis region in suspected infective endocarditis (SUVmax and TBR = SUVmax valve/prosthesis / SUVmean blood pool).

Time frame: Visit 2 (baseline imaging), performed within 14 days of enrolment and no later than 14 days after initiation of intravenous antibiotic therapy.

Secondary Outcomes

Diagnostic performance of Al[¹⁸F]F-NOTA-folate PET for cardiac sarcoidosis and native or prosthetic valve infective endocarditis

Time frame: From enrollment to study completion at 2 years.

Change in myocardial Al[¹⁸F]F-NOTA-folate uptake following immunosuppressive therapy in cardiac sarcoidosis

Patients with confirmed CS may undergo optional follow-up static PET imaging with Al\[¹⁸F\]F-NOTA-folate and \[¹⁵O\]water approximately 3 months after baseline imaging to assess changes in inflammatory activity following initiation of immunosuppressive therapy.

Time frame: From Visit 2 (baseline imaging) to Visit 3 (follow-up imaging). Visit 2 is performed 7 days after initiation of systemic immunosuppressive therapy and Visit 3 is performed approximately 3 months after baseline imaging.

Biodistribution and radiation dosimetry of Al[¹⁸F]F-NOTA-folate

Healthy volunteers will undergo extended imaging, including dynamic imaging for 120 min starting at the time of tracer injection + static imaging for 10 minutes at 150 min after tracer injection to support analysis of tracer kinetics and biodistribution, and radiation dosimetry calculations.

Time frame: Visit 2 (imaging), performed 7-14 days after Visit 1 (screening and enrolment).

Incidence and severity of adverse events related to Al[¹⁸F]F-NOTA-folate

Incidence and severity of adverse events (AE) and adverse reactions; clinically significant changes in vital signs or ECG; changes in safety laboratory parameters (healthy volunteers); clinically indicated laboratory assessments performed in the event of an adverse event (as applicable); and investigator assessment of relationship to Al\[¹⁸F\]F-NOTA-folate.

Time frame: Suspected sarcoidosis and infective endocarditis groups: from Visit 2 (baseline imaging) to study completion at 2 years. Healthy volunteers: from Visit 2 to 48-72 hours, when safety laboratory tests will be obtained and AEs assessed by phone interview.