A comparative evaluation of conventional and pretargeted radioimmunotherapy of CD20-expressing lymphoma xenografts.

Abstract

Radioimmunotherapy with anti-CD20 monoclonal antibodies is a promising new treatment approach for patients with relapsed B-cell lymphomas. However, the majority of patients treated with conventional radiolabeled anti-CD20 antibodies eventually have a relapse because the low tumor-to-blood and tumor-to-normal organ ratios of absorbed radioactivity limit the dose that can be safely administered without hematopoietic stem cell support. This study assessed the ability of a streptavidin-biotin "pretargeting" approach to improve the biodistribution of radioactivity in mice bearing Ramos lymphoma xenografts. A pretargeted streptavidin-conjugated anti-CD20 1F5 antibody was infused, followed 24 hours later by a biotinylated N-acetylgalactosamine-containing "clearing agent" and finally 3 hours later by (111)In-labeled DOTA-biotin. Tumor-to-blood ratios were 3:1 or more with pretargeting, compared with 0.5:1 or less with conventional (111)In-1F5. Tumor-to-normal organ ratios of absorbed radioactivity up to 56:1 were observed with pretargeting, but were 6:1 or less with conventional (111)In-1F5. Therapy experiments demonstrated that 400 microCi (14.8 MBq) or more of conventional (90)Y-1F5 was required to obtain major tumor responses, but this dose was associated with lethal toxicity in 100% of mice. In marked contrast, up to 800 microCi (29.6 MBq) (90)Y-DOTA-biotin could be safely administered by the pretargeting approach with only minor toxicity, and 89% of the mice were cured. These data suggest that anti-CD20 pretargeting shows great promise for improving current therapeutic options for B-cell lymphomas and warrants further preclinical and clinical testing.

• Authors: O W Press, M Corcoran, K Subbiah, D K Hamlin, D S Wilbur, T Johnson, L Theodore, E Yau, R Mallett, D L Meyer, D Axworthy
• Journal: Blood (Blood) Vol. 98 Issue 8 Pg. 2535-43 (Oct 15 2001) ISSN: 0006-4971 [Print] United States
• PMID: 11588052 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Antigens, CD20
• Iodine Radioisotopes

Topics

• Animals
• Antibodies, Monoclonal (therapeutic use)
• Antigens, CD20 (immunology)
• Disease Models, Animal
• Humans
• Iodine Radioisotopes (pharmacokinetics, therapeutic use)
• Lymphoma, B-Cell (radiotherapy)
• Mice
• Mice, Nude
• Radioimmunotherapy (methods)
• Survival Rate
• Tissue Distribution
• Transplantation, Heterologous
• Tumor Cells, Cultured