Ex vivo characterization of transthyretin cardiac amyloidosis (TTR-CA) using an amyloid β specific PET imaging agent. Preliminary data

Objectives Familial amyloid polyneuropathy is a hereditary form of amyloidosis due to a mutated variant of transthyretin (TTR) produced by the liver. Cardiac involvement is characterized by extracellular depositions of amyloid β (Aβ) which can lead to heart failure, conduction disturbances, arrhythmias and sudden death. While early diagnosis of Transthyretin cardiac amyloidosis (TTR-CA) has important therapeutic and prognostic impact, there is no sensitive and quantitative tool to document the location and extent of cardiac Aβ in these patients. So we aimed to test ex vivo the usefulness of ¹⁸F-AV45, a high specific Aβ PET tracer recently FDA approved in Alzheimer’s disease.

Methods Binding of ¹⁸F-AV45 to Aβ was evaluated by autoradiography in myocardial tissue obtained from patients who underwent cardiac transplantation either for TTR-CA, or ischemic heart failure (controls). Frozen heart sections (20μm-thickness, n=2 for each data point) were incubated with ¹⁸F-AV45 at concentrations of 1 or 3nM. Nonspecific binding was assessed by incubation of adjacent sections in the presence of an excess (300μM) of cold AV45. After the film was developed, images were scanned and analysed by grey-level semi-quantification process using βvision+ software.

Results ¹⁸F-AV45 uptake was significantly higher in TTR-CA myocardial sections when compared to controls (+70%±10%). The intensity of ¹⁸F-AV45 binding markedly decreased in sections incubated with unlabeled AV45 (-83%±5%), strongly suggesting Aβ specificity.

Conclusions These preliminary data demonstrate ¹⁸F-AV45 capability to bind specifically Aβ in heart tissue, and provide the basis for a clinical trial designed to determine its diagnostic potential in TTR-CA patients.