Molecular Imaging of Systemic and Cardiac Amyloidosis: Recent Advances and Focus on the Future

Autopsy-derived myocardial sections showing specific binding of ¹⁸F-florbetapir with myocardial AL and ATTR deposits. These autoradiography results confirm specific binding of ¹⁸F-florbetapir to ATTR (top row) and AL (middle row) deposits on myocardial sections and no binding to control myocardium (bottom row). Minimal to no nonspecific binding was seen (right column). (Reprinted with permission of (19).)

Myocardial retention of ¹⁸F-florbetapir in CA and control cohorts. RI of ¹¹C-PiB (A) and ¹⁸F-florbetapir (B) in myocardium was significantly higher in amyloidosis cohort than in control cohort, with no overlap in 95% CIs. p.i. = after injection. (A and B reprinted with permission of (26) and (27), respectively.)

Myocardial uptake of amyloid PET radiotracers ¹⁸F-florbetapir (A), ¹¹C-PiB (B), and ¹⁸F-florbetaben (C and D) in AL CA, ATTR CA, and control cohorts. Small cohort studies from multiple centers showed that amyloid tracer retention in heart is highest in AL CA cohort, intermediate in ATTR CA cohort, and lowest in control cohorts. These findings suggest lower binding affinity of β-amyloid tracers to ATTR deposits than to AL deposits. (Reprinted with permission of (23,27,29,54).

Comparison of myocardial uptake of ¹²⁴I-evuzamitide and ¹⁸F-florbetapir in same cohort of patients with AL CA and ATTR CA. All other measures of amyloid, left ventricular (LV) percentage injected dose (%ID), SUV_mean, and cardiac amyloid activity (CAA) were higher in ATTR CA with ¹²⁴I-evuzamitide, except for LV target-to-background ratio (TBR), which was higher with ¹⁸F-florbetapir. CMP = cardiomyopathy. (Reprinted with permission of (30).)

Myocardial (top 2 rows) and systemic organ (bottom row) uptake of ¹⁸F-florbetapir and ¹²⁴I-evuzamitide in patients with various forms of amyloidosis. Liver uptake is physiologic on ¹⁸F-florbetapir imaging. Amyloid PET tracers bind to various types of amyloid and can image amyloid deposits in heart as well as in certain systemic organs. Apo-A-IV = apolipoprotein AIV.

Diagnosis of preclinical AL CA using ¹⁸F-florbetapir PET/CT. Shown are ¹⁸F-florbetapir myocardial RI in AL CA (left dot plot, AL cardiomyopathy, untreated), AL CA with successful AL amyloidosis therapy and hematologic remission for >1 y (middle dot plot, AL remission cardiomyopathy), and systemic AL amyloidosis patients with normal left ventricular wall thickness and normal cardiac biomarkers (right dot plot, AL before cardiomyopathy). Dotted lines indicate normal limits derived from healthy controls. About half of patients in AL-before-cardiomyopathy cohort showed abnormally elevated myocardial ¹⁸F-florbetapir RI values, which were similar to those of patients with clinically documented AL cardiomyopathy. Panel on right shows images from 2 patients with AL before cardiomyopathy, one with significant myocardial uptake of ¹⁸F-florbetapir (PET-positive) and another with no uptake (PET-negative). These findings suggest that ¹⁸F-florbetapir can identify early preclinical AL amyloid deposits in myocardium. (Reprinted with permission of (42).)