Real-Time PET Imaging with Amyloid Fibril-Reactive Antibody CAEL-101 for Personalized AL Amyloidosis Immunotherapy

Mortality of light-chain (AL) amyloidosis remains high due to multi-organ dysfunction caused by persistent, insoluble amyloid fibril deposits. The amyloid fibril-reactive murine monoclonal antibody 11-1F4 directly binds to a conformational epitope on light-chain amyloid fibrils in mice and was successfully used as imaging tool in human (AM J Pathol. 157:1239; Blood. 116: 2241). The chimeric form of 11-1F4 (CAEL-101) demonstrated therapeutic potential in a phase 1a/b study where 67% of patients with cardiac or renal amyloidosis showed organ response (Blood 130:509) and 9/10 cardiac amyloidosis patients showed improvement of the Global Longitudinal Strain (Blood 132:958). Inspired by the promising data, the overall goal of this work is to establish an optimal CAEL-101 PET probe as a potential imaging tool for the diagnosis and stratification of patients with systemic AL amyloidosis.