Molecular imaging of amyloidosis: Will the heart be the next target after the brain?

Learning Objectives 1. To review the pathophysiology, classification, diagnosis and treatment of amyloidosis with emphasis on cardiac amyloidosis. 2. To summarize radiotracers currently used in clinical study for cardiac amyloidosis imaging. 3. To discuss the rational to extend the use of brain amyloid beta PET tracers to cardiac amyloidosis imaging.

Amyloidosis refers to extracellular depositions of insoluble fibrillar amyloids in organs, and can be classified by the precursor proteins into: 1. primary amyloidosis (or light-chain amyloidosis, AL), 2. secondary amyloidosis (or reactive amyloidosis, AA), 3. transthyretin related amyloidosis (ATTR) including senile systemic amyloidosis (SSA) and hereditary amyloidosis(or familial amyloidosis, FA), and hemodialysis-related amyloidosis (beta2-microglobulin). For the heart, only AL and ATTR cause clinically significant heart disease. Early diagnosis of cardiac amyloidosis, and more importantly, the identification of the type of amyloid have important clinical, therapeutic and prognostic implications; e.g. chemotherapy and stem cell transplantation for AL versus liver transplantation for ATTR. For nuclear imaging of cardiac amyloidosis, radiotracers can be grouped into three major categories: 1. bone seeking tracers, such as 99mTc-PYP, 99mTc-MDP and 99mTc-DPD, 2. non-bone seeking tracers, and 3. derivatives of thioflavin-T developed for brain amyloid beta imaging. Although promising, results from bone seeking tracers are conflicting with variations in terms of diagnostic performance, except for 99mTc-DPD, which may have a potential role in differentiation of AL from ATTR cardiac amyloidosis. Non-bone seeking radiotracers such as 123I labeled amyloid P component (123I-SAP), 123I-mIBG, 99mTc-aprotinin, and 111In or 124I labeled amyloid antibodies have also shown some success in identifying cardiac amyloidosis. The future, however, may lie in derivatives of thioflavin-T, such as 18F-Florbetapir, which has been recently approved by FDG for visualization of amyloid beta in the brain of patients with Alzheimer’s disease