Biodistribution of a novel radiolabeled fibril-reactive monoclonal antibody in patients with systemic light chain (AL) amyloidosis

Objectives To quantify the post-infusion biodistribution of ¹²⁴I-labeled murine mAb 11-1F4 in patients with AL amyloidosis, using organ-specific PET time activity curves (TAC).

Methods Initially 3 patients with AL amyloidosis were imaged by PET/CT at multiple time points (1 min to 10 d) post administration of radiotracer (RT). Subsequently 15 patients were imaged 2 and 5 days post RT. Biodistribution was assessed with TAC using decay-corrected mean activity (Bq/ml) in regions of interest defining blood pool and individual organs. Ratios of organ-specific activity to blood pool activity and to organs not clinically involved with amyloid (lung and skeletal muscle) were calculated.

Results The TAC demonstrated variability in radiotracer biodistribution among patients, likely due to differences in location and extent of pathologic amyloid deposits. The ratio of radiotracer uptake to blood pool activity proved helpful to define uptake in organs and for comparison of RT uptake between patients. Notably, there was marked and persistent increased organ-specific uptake of the radiolabeled mAb in 9 patients (spleen, liver, lymph nodes, adrenal, and bone marrow) on TAC, indicating binding of RT to pathologic sites of fibril deposition.

Conclusions Characterization of the biodistribuation of ¹²⁴I-labeled fibril reactive mAb 11-1F4 in patients with AL amyloidosis has (1) demonstrated variability between patients and (2) defined organ specific uptake. Quantitative analysis is a useful method to document and quantify the extent of amyloid deposits as well as to identify patients who are candidates for immunotherapy using a chimeric form of this antibody. Additionally, radioimmunoimaging can provide a quantitative method for monitoring therapeutic response or disease progression.

Research Support USPHS Research Grant R01CA10056 and FDA Orphan Product Development Grant FD-R-00342