Molecular Imaging of Amyloidosis: Will the Heart Be the Next Target After the Brain?

Amyloidosis is a heterogeneous group of diseases with a common feature of extracellular deposition and infiltration of different types of amyloid fibrils in various organs. For example, Alzheimer’s disease is characterized by deposition of amyloid β in the brain. Radiolabeled positron emission tomography (PET) tracers, mainly derivatives of thioflavin-T, were recently introduced for identification of amyloid β plaques in Alzheimer’s patients. Such advances of amyloid β plaque imaging of the brain may shed light into imaging of other organs in amyloidosis patients, such as the heart. Cardiac infiltration of amyloid confers poor clinical outcomes, which renders early diagnosis for appropriate clinical management. At present, nuclear imaging of cardiac amyloidosis is predominantly accomplished with bone-seeking radiotracers, such as 99m-technetium-labeled pyrophosphate (^99mTc-PYP), 99m-technetium-methylene diphosphonate (^99mTc-MDP), and 99m-technetium-3,3,-diphosphono-1,2-propanodicarboxylic acid (^99mTc-DPD), with conflicting results in terms of diagnostic performance, with the exception for ^99mTc-DPD, which may differentiate light-chain amyloidosis from transthyretin-related cardiac amyloidosis. Although other non–bone-seeking radiotracers such as iodine-123-labeled amyloid P component (¹²³I-SAP), 123-iodine-Meta-iodobenzylguanidine (¹²³I-mIBG), 99m-technetium-labeled protease inhibitor, and indium-111-labeled amyloid antibodies have also shown some success in identifying cardiac amyloidosis, the future, however, may lie in labeling derivatives of thioflavin-T. With the recent success of visualizing deposition of amyloid β in the brain, the US Food and Drug Administration–approved PET imaging agent ¹⁸F-florbetapir may be used to target cardiac amyloidosis next.