Assessment of 18F-Florbetaben Whole-body PET for the Detection of Cardiac and Extracardiac Sites of Amyloid Deposits

• Status: Recruiting
• Trial end date: 2021-12-31
• Target enrollment: 0
• Participant gender: All

Summary

Although being classified as a rare disease, cardiac amyloidosis constitutes an increasing cause of heart failure, which is often overlooked and thus poorly managed. Amyloidosis involves deposits of light chain immunoglobulins in the immunoglobulin light chain amyloidosis (AL) type, but it may also be of a hereditary type in mutated transthyretin amyloidosis (ATTRm) or of a senile type in wildtype transthyretin forms (ATTRwt).

Myocardial biopsy remains a gold standard for definitive diagnosis but it is a traumatic technique which only provides information on a limited number of sampled sites.

Useful but not fully specific signs of cardiac amyloidosis may also be provided by Magnetic Resonance Imaging or MRI (delayed retention imaging) and echocardiography (longitudinal strain pattern).

Notwithstanding the above, relatively specific markers of amyloid plaques are now available in Positron Emission Tomography (PET). These markers are primarily fluorinated tracers which have been developed for the diagnosis of Alzheimer's disease. Two of these have already been the subject of feasibility studies in the setting of cardiac amyloidosis diagnosis, on a maximum of 10 amyloidosis patients but with very favorable results.

The hypothesis is that one of these two tracers, Florbetaben labelled with Fluorine-18-Florbetaben (18F-Florbetaben) used in the study, has sufficiently strong and prolonged binding kinetics at the level of the amyloid plaques to allow: (i) achieving whole-body PET recordings and thus, (ii) identifying not only cardiac amyloidosis but also extracardiac binding sites, particularly those readily accessible to biopsy sampling. This hypothesis has been strengthened by a recent case report illustrating the ability of whole-body florbetaben-PET to image not only cardiac but also extra-cardiac sites of amyloid deposits (Clin Nucl Med. 2017;42(1):50-3).

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Central Hospital, Nancy, France

Criteria

Inclusion Criteria:

• For all study participants

1. Person affiliated to or beneficiary of, a social security plan

2. Person informed about study organization and having signed the informed consent

• For ATTR amyloidosis patients:

1. left ventricular concentric hypertrophy with a diastolic septal thickness ≥ 15 mm at echography (as defined by the current distribution of this parameter in the ATTR patients involved in a French national cohort of the Henri Mondor Hospital),

2. clearly positive bone scan (> mild cardiac uptake) and/or concordant results at pathology of cardiac or extra-cardiac sites (Congo red-positive deposits under crossed polarized light and immunohistochemical staining for transthyretin).

• For AL amyloidosis patients:

1. left ventricular concentric hypertrophy with a diastolic septal thickness ≥ 13 mm at echography (as defined by the current distribution of this parameter in the AL patients involved in the French national cohort of the Henri Mondor Hospital),

2. significant cardiac disease evidenced by an increase in plasma N-Terminal ProBNP (or BNP) and/or in troponin T (or I), corresponding to a Mayo clinic score ≥ 2 ,

3. concordant results at pathology of cardiac or extra-cardiac sites (Congo red-positive deposits under crossed polarized light and immunohistochemical staining for κ and λ immunoglobulin light chains).

• For control subjects:

1. History of surgical or Transcatheter Aortic Valve Implantation (TAVI)treatment of aortic stenosis

2. Matching with amyloidosis patients according to gender and age (± 5 years).

3. Cardiac hypertrophy with a diastolic septal thickness ≥ 15 mm at echography when matching with an ATTR patient and ≥ 13 mm when matching with an AL patient.

Exclusion Criteria:

1. Known allergy to the active substance and to any excipient for 18F-Florbetaben or for the bone scintigraphy radiotracer (99mTc-MDP)

2. Pregnancy, breastfeeding and woman of childbearing age without effective contraception

3. Person referred in articles L.1121-5 to L.1121-8 and L.1122-2 of the Public Health Code:

• Pregnant, parturient or breastfeeding woman

• Person deprived of liberty for judicial or administrative decision

• Person under psychiatric care

• Person admitted to health or social institution for other reasons than research

• Minor person (non-emancipated)

• Adult person under legal protection (any form of public guardianship)

• Adult person incapable of giving consent and not under legal protection

4. No obvious cause of cardiac disease except for mild to moderate hypertension in all study subjects, for cardiac amyloidosis in the amyloidosis groups and for aortic stenosis in the control group

5. Impossibility of performing 18F-Florbetaben PET (agitated, confused patient, etc.).

6. Sever left ventricular dysfunction with an ejection fraction ≤ 35%

7. Severe hepatic or renal failure.

8. For control patients only: monoclonal gammopathy on a previous protein electrophoresis or ≥ mild cardiac uptake on a previous bone scintigraphy.