Early Detection of Amyloidosis in Monoclonal Gammopathy Using Nuclear Medicine Imaging (MGUS-PET)

Aim of the Project: The overarching goal is to establish a non-invasive, sensitive method for early detection of systemic amyloid deposits, laying the foundation for earlier diagnosis and improved treatment of AL amyloidosis.

• Primary Aim: Validate 18F-florbetaben PET for detection of systemic AL amyloidosis versus negative controls.
• Secondary Aim: Compare the sensitivity of amyloid PET with established methods (echocardiography, MRI, serological biomarkers) for the detection of early organ involvement.
• Tertiary Aim: Quantify and characterize systemic amyloid burden across early and manifest disease stages.

Hypotheses:

1. Amyloid PET shows pathological tracer uptake in patients with AL amyloidosis and remains unremarkable in negative controls.
2. Amyloid PET detects amyloid deposits at a stage in which conventional methods do not yet show structural or functional changes.
3. Systemic amyloid burden follows a graded pattern, with intermediate values in early disease and the highest values in manifest AL amyloidosis.

Study Design and Methods Prospective, observational cohort study at the University Hospital Zurich (USZ). 50 participants will be recruited from the established COSMO-AL cohort at the Department of Hematology, which systematically captures patients with clinically significant monoclonal gammopathy and provides standardized skin biopsy data.

Participants:

• Negative controls: monoclonal gammopathy without histologic amyloid (n = 10).
• Early disease (study cohort): monoclonal gammopathy with local, histologically confirmed amyloid deposits (n = 20).
• Positive controls: biopsy-confirmed systemic AL amyloidosis (n = 20). Patients with confirmed amyloid involvement will be additionally stratified by organ involvement to allow exploratory analysis of organ-specific tracer uptake.