[18F]-Florbetaben PET/CT for Differential Diagnosis Among Cardiac Immunoglobulin Light Chain, Transthyretin Amyloidosis, and Mimicking Conditions

Objectives: This study aimed to test the diagnostic value of [18F]–florbetaben positron emission tomography (PET) in patients with suspicion of CA. Background: Diagnosis of cardiac involvement in immunoglobulin light-chain–derived amyloidosis (AL) and transthyretin-related amyloidosis (ATTR), which holds major importance in risk stratification and decision making, is frequently delayed. Furthermore, although diphosphonate radiotracers allow a noninvasive diagnosis of ATTR, demonstration of cardiac amyloidosis (CA) in AL may require endomyocardial biopsy. Methods: Forty patients with biopsy-proven diagnoses of CA (20 ALs, 20 ATTRs) and 20 patients referred with the initial clinical suspicion and later diagnosed with non-CA pathology underwent a cardiac PET/computed tomography scan with a 60-min dynamic [18F]-florbetaben PET acquisition, and 4 10-min static scans at 5, 30, 50, and 110 min after radiotracer injection. Results: Visual qualitative assessment showed intense early cardiac uptake in all subsets. Patients with AL displayed a high, persistent cardiac uptake in all the static scans, whereas patients with ATTR and those with non-CA showed an uptake decrease soon after the early scan. Semiquantitative assessment demonstrated higher mean standardized uptake value (SUVmean) in patients with AL, sustained over the whole acquisition period (early SUVmean: 5.55; interquartile range [IQR]: 4.00 to 7.43; vs. delayed SUVmean: 3.50; IQR: 2.32 to 6.10; p = NS) compared with in patients with ATTR (early SUVmean: 2.55; IQR: 1.80 to 2.97; vs. delayed SUVmean: 1.25; IQR: 0.90 to 1.60; p < 0.001) and in patients with non-CA (early SUVmean: 3.50; IQR: 1.60 to 3.37; vs. delayed SUVmean: 1.40; IQR: 1.20 to 1.60; p < 0.001). Similar results were found comparing heart-to-background ratio and molecular volume. Conclusions: Delayed [18F]-florbetaben cardiac uptake may discriminate CA due to AL from either ATTR or other mimicking conditions. [18F]-florbetaben PET/computed tomography may represent a promising noninvasive tool for the diagnosis of AL amyloidosis, which is still often challenging and delayed. (A Prospective Triple-Arm, Monocentric, Phase-II Explorative Study on Evaluation of Diagnostic Efficacy of the PET Tracer [18F]-Florbetaben [Neuraceq] in Patients With Cardiac Amyloidosis [FLORAMICAR2]; EudraCT number: 2017-001660-38)