Visualizing systemic light chain amyloidosis with 18f-flutemetamol PET/CT: Correlation with biomarkers and clinical outcome

Abstract Background: Immunoglobulin light chain (AL) amyloidosis is a monoclonal plasma cell disorder characterized by the pathological production of nonfunctional immunoglobulin light chains that misfold and form β-pleated amyloid fibrils. Positron emission tomography (PET)/computed tomography (CT) with 18F-flutemetamol (FMM) is a noninvasive imaging modality developed for visualization of the deposition of β-amyloid plaques in the brain. This study aimed to assess the value of FMM PET/CT in patients with AL amyloidosis. Methods: Patients with known or clinically suspected AL amyloidosis were prospectively enrolled from 2022 to 2024 at a single institution (Seoul St. Mary's Hospital). FMM PET/CT images were obtained from the vertex of skull to the upper thighs, and organs with positive FMM uptake were noted and measured. Age, gender, and lab results such as N-terminal pro-brain natriuretic peptide (NT-proBNP), troponin I (TnI), creatinine (Cr), glomerular filtration rate (GFR), protein-to-creatinine ratio (PCR), albumin-to-creatinine ratio (ACR), alkaline phosphatase (ALP), and gamma-glutamyl transpeptidase (GTP) were collected. The image findings were compared to the clinical parameters and analyzed for survival outcome. Results: Of 45 consecutive patients with AL amyloidosis, 9 patients who did not receive treatment or were not followed up were excluded, and a total 36 patients with histologically proven AL amyloidosis were included for analysis (22 male, 14 female; median age 66 years). All but one patient with equivocal finding in the kidneys showed positive FMM uptake in one or more organs on FMM PET/CT. Twenty-one (58%) had cardiac involvement on FMM PET/CT. Twenty-two (61%) had positive findings in 4 or more organs other than the heart. The maximum standard uptake value (SUVmax) of the myocardium ranged from 0.7 to 10.5 (mean±SD, 2.9±2.6), and showed positive correlation (Spearman correlation) with NT-proBNP (r=0.57, p<0.001) and TnI (r=0.60, p<0.001). The SUVmax of the kidneys and the lab findings of renal function were not correlated. After chemotherapy, all patients exhibited hematologic response: 1 stringent complete response (CR), 12 CR, 5 very good partial response (PR), 17 PR, and 1 minimal response. Fourteen (39%) patients died during the follow period of up to 38.6 months. The FMM PET/CT was positive for myocardial involvement in all but one patient among those who expired (13/14, 93%), compared to 8/22 (36%) of surviving patients. Significantly increased risk for death (univariate cox regression) was observed in patients with elevated NT-proBNP (p<0.001), elevated TnI (p=0.02), increased myocardial FMM uptake (p=0.018) and increased FMM uptake in 4 or more organs (p=0.045). Age, gender, and other laboratory findings were not associated with OS. On multivariate cox regression analysis, NT-proBNP was the parameter with the strongest prognostic value for OS. Even in cases with relatively low NT-proBNP levels, positive cardiac uptake on FMM PET/CT was associated with risk of death. Conclusion: FMM PET/CT allowed visualization of systemic involvement in 97% of the patients with AL amyloidosis. Quantitative FMM measurement in the myocardium was significantly correlated to NT-proBNP and Tnl values. Positive finding in the heart and involvement of multiple organs on FMM PET/CT were associated with worse OS.