Radioimmunodetection of amyloid deposits in patients with AL amyloidosis
- 30 September 2010
- journal article
- Published by American Society of Hematology in Blood
- Vol. 116 (13), 2241-2244
- https://doi.org/10.1182/blood-2010-03-273797
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 124I-mAb m11-1F4 can be used to identify AL candidates for passive immunotherapy using the chimeric form of the antibody. This trial was registered at www.clinicaltrials.gov as NCT00807872.Keywords
This publication has 21 references indexed in Scilit:
- Splenic plasma cells can serve as a source of amyloidogenic light chainsBlood, 2009
- Immunodiagnostic Capabilities of Anti–Free Immunoglobulin Light Chain Monoclonal AntibodiesAmerican Journal of Clinical Pathology, 2008
- Long-term outcome of patients with AL amyloidosis treated with high-dose melphalan and stem-cell transplantationBlood, 2007
- Phage Display and Peptide Mapping of an Immunoglobulin Light Chain Fibril-Related Conformational EpitopeBiochemistry, 2007
- Localization of a Conformational Epitope Common to Non-Native and Fibrillar Immunoglobulin Light ChainsBiochemistry, 2007
- Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): A consensus opinion from the 10th International Symposium on Amyloid and AmyloidosisAmerican Journal of Hematology, 2005
- Immunotherapy in Systemic Primary (AL) Amyloidosis Using Amyloid-Reactive Monoclonal AntibodiesCancer Biotherapy & Radiopharmaceuticals, 2003
- Molecular Mechanisms of AmyloidosisThe New England Journal of Medicine, 2003
- Antibody-Mediated Resolution of Light Chain-Associated Amyloid DepositsThe American Journal of Pathology, 2000
- Protein and host factors implicated in the pathogenesis of light chain amyloidosis (AL amyloidosis)Amyloid, 1995