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Preclinical evaluation of 90Y-labeled anti-CD20 monoclonal antibody for treatment of non-Hodgkin's lymphoma



Preclinical evaluation of 90Y-labeled anti-CD20 monoclonal antibody for treatment of non-Hodgkin's lymphoma



International Journal of Oncology 15(5): 1017-1025



A high-affinity IgG1 kappa murine monoclonal anti-CD20 antibody (IDEC-2B8) was developed for radioimmunotherapy of non-Hodgkin's B-cell lymphoma. A stable immunoconjugate (Zevalintrade mark) was prepared by reacting IDEC-2B8 with a derivative of diethylenetriaminepentaacetic acid, designated MX-DTPA, a chelator exhibiting high affinity and retention for 90Y. Zevalin exhibited antigen specificity, human tissue reactivity, and preclinical safety profile comparable to the native antibody. The conjugate radiolabeled with 90Y (90Y-Zevalin) or 111In (111In-Zevalin) exhibited excellent retention of immunoreactivity with radioincorporations >95%. The radiolabeled conjugates formulated in PBS containing human serum albumin were stable in vitro at 4 degrees C for 48 h as indicated by negligible loss of radioisotope and retention of binding to CD20+ cells. In vitro human serum stability studies at 37 degrees C with 90Y-Zevalin indicated that loss of 90Y from the conjugate was minimal, averaging 1% per day. Biodistribution studies in BALB/c mice confirmed the in vitro stability of 90Y-Zevalin and 111In-Zevalin. In particular, excellent in vivo retention of 90Y by the conjugate was demonstrated by minimal bone accumulation (

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Accession: 011180006

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PMID: 10536187

DOI: 10.3892/ijo.15.5.1017



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