Autor: |
Vallera DA; Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Cancer Center, Minneapolis, MN, USA. valle001@tc.umn.edu, Elson M, Brechbiel MW, Dusenbery KE, Burns LJ, Jaszcz WB, Ramsay NK, Panoskaltsis-Mortar A, Kuroki DW, Wagner JE, Vitetta ES, Kersey JH |
Jazyk: |
angličtina |
Zdroj: |
Cancer biotherapy & radiopharmaceuticals [Cancer Biother Radiopharm] 2004 Feb; Vol. 19 (1), pp. 11-23. |
DOI: |
10.1089/108497804773391630 |
Abstrakt: |
Studies were performed to determine the suitability of using two different anti-CD19 monoclonal antibodies to deliver the high energy beta-particle emitting isotope 90Y to B-cell lymphoma grown as flank tumors in athymic nude mice. The antibodies BU12 and HD37, both of the IgG1 subclass, recognize CD19, an internalizing B-lineage-specific membrane glycoprotein and member of the Ig supergene family. The antibodies were readily labeled with 90Y using the highly stable chelate, 1B4M-MX-DTPA. The radioimmunoconjugates selectively bound to the CD19 expressing B cell line Daudi, but not to CD19 negative control cells. Significantly more 90Y anti-CD19 bound to Daudi tumors growing in nude mice than did a control non-binding antibody (p = 0.001). The biodistribution data correlated with an anti-tumor effect. Anti-tumor activity was dose dependent and the best results were observed in mice receiving a single dose of approximately 300 uCi. The anti-CD19 antibody had significantly better anti-tumor activity as compared to a control 90Y-labeled antibody and most mice survived over 119 days with no evidence of tumor (p < 0.003). Histology studies showed no significant injury to the kidney, liver, or small intestine. Because radiolabeled anti-CD19 antibody can be used to deliver radiation selectively to lymphohematopoietic tissue, these data support the use of 90Y anti-CD19 antibodies in treating B-cell malignancies. |
Databáze: |
MEDLINE |
Externí odkaz: |
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