Radioimmunodetection of amyloid deposits in patients with AL amyloidosis

Abstract

Care of patients with AL amyloidosis currently is limited by the lack of objective means to document disease extent, as well as therapeutic options that expedite removal of pathologic deposits. To address these issues, we have initiated a Phase I Exploratory IND study to determine the biodistribution of the fibril-reactive, amyloidolytic murine IgG1 mAb 11-1F4 labeled with I-124. Patients were infused with less than 1 mg (∼ 74 MBq) of GMP-grade antibody and imaged by PET/CT scan 48 and 120 hours later. Among 9 of 18 subjects, there was striking uptake of the reagent in liver, lymph nodes, bone marrow, intestine, or, unexpectedly, spleen (but not kidneys or heart). Generally, positive or negative results correlated with those obtained immunohistochemically using diagnostic tissue biopsy specimens. Based on these findings, we posit that (124)I-mAb m11-1F4 can be used to identify AL candidates for passive immunotherapy using the chimeric form of the antibody.

Trial registration: ClinicalTrials.gov NCT00807872.

Figures

Figure 1

Radioimmunoimaging and immunohistochemical detection of AL amyloid. Three patients with systemic AL amyloidosis (AL 2, AL 11, AL 12) received an intravenous infusion of approximately 2 mCi (1 mg) of 124I-labeled m11-1F4. (A) Fused coronal and sagittal PET/CT images acquired 5-days after infusion using the high-resolution Siemens Biograph 16 (patient AL 2) or molecular CT (patients AL 11, AL 12) instruments. (B) Maximum intensity projection PET images. (C) Polarizing and light microscopy. Consecutive tissue sections from each patient (AL 2, lymph node; AL 11, bone marrow, and AL 12, liver) were subjected to histochemical (HC) staining with Congo red (CR, top) or immunohistochemical (IHC) studies using, as primary reagent, mAb 11-1F4 (middle), or, as a negative control, the antibody preincubated with a 22-mer peptide containing the conformational fibril-related epitope recognized by mAb 11-1F4 (bottom). Photomicrographs were acquired with a Leica DM 500 light microscope equipped with cross-polarizing filters. Digital images were obtained using a cooled charged coupled device camera and dedicated SPOT software (Version 3.5.2) at an original magnification × 160.