Early Detection of Amyloidosis in Monoclonal Gammopathy Using Nuclear Medicine Imaging

Early Detection of Light-Chain Amyloidosis in Monoclonal Gammopathy Using 18F-Florbetaben PET/MR: a Prospective, Single-Center, Observational Study

The goal of this clinical trial is to evaluate whether ¹⁸F-florbetaben PET/MR can detect systemic amyloid deposits early and noninvasively in patients with monoclonal gammopathy. The main question it aims to answer is: Can ¹⁸F-florbetaben PET/MR identify systemic amyloid deposits across clinically and histologically defined patient groups?

Participants will:

• Be screened for eligibility and asked to sign an informed consent form
• Have their vital signs measured
• Receive a single intravenous injection of approximately 300 MBq ¹⁸F-florbetaben (Neuraceq®), followed by whole-body PET/MR imaging from skull base to below the kidneys. If MRI is contraindicated (e.g., pacemaker, severe claustrophobia), PET/CT will be performed instead. The scan takes approximately one hour, during which participants lie still in the scanner
• Be monitored during and after the scan for any side effects or adverse events
• Complete study participation at the end of the imaging session (single visit, no follow-up required)

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.

Inclusion Criteria:

• Participation in the COSMO-AL study
• Available biopsy test result
• Written informed consent

Exclusion Criteria:

• Pregnant or lactating women