Successful therapy of a human lung cancer xenograft using MAb RS7 labeled with residualizing radioiodine.

Abstract

We have recently reported that a radioiodinated, DTPA-appended peptide, designated IMP-R1, is a residualizing iodine label that overcomes many of the limitations that have impeded the development of residualizing iodine for clinical use. In this study the potential of 131I-IMP-R1-RS7, an internalizing anti-EGP-1 monoclonal antibody, was evaluated by performing preclinical therapy studies in nude mice bearing Calu-3 human non-small cell carcinoma of the lung xenografis. Elimination of 6 of 9 established tumors (mean tumor volume=0.3 cm(3)) was observed using a single dose of 350 microCi/mouse of 131I-IMP-R1-RS7, with all animals tolerating the dose. At the same dose and specific activity of 131I-RS7, labeled using the conventional chloramine-T method, there were four deaths, and one complete remission in nine treated mice. At the maximum tolerated dose of conventionally 131I-labeled RS7, 275 microCi, mean stable disease for approximately 5 weeks was observed, with no complete responses. Specificity of the therapeutic effect was shown in an isotype-matched control experiment, where 131I-IMP-R1-RS7 was markedly more effective than the (131)I-IMP-R1-labeled control antibody. These studies demonstrate that (131)I-IMP-R1-RS7 provides a therapeutic advantage in comparison to conventional 131I-labeled RS7, as predicted by the increased tumor accretion observed previously in targeting studies. A direct comparison of the maximum tolerated doses of (131)I-IMP-R1-RS7 (350 microCi) and 90Y-DOTA-RS7 (105 microCi) was performed in this tumor model using large established tumors (mean tumor volume=0.85 cm(3)). Anti-tumor efficacy and toxicity of the two treatments were comparable.

• Authors: R Stein, S V Govindan, S Chen, L Reed, H Spiegelman, G L Griffiths, H J Hansen, D M Goldenberg
• Journal: Critical reviews in oncology/hematology (Crit Rev Oncol Hematol) 2001 Jul-Aug Vol. 39 Issue 1-2 Pg. 173-80 ISSN: 1040-8428 [Print] Netherlands
• PMID: 11418314 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Iodine Radioisotopes
• Membrane Proteins

Topics

• Animals
• Antibodies, Monoclonal (administration & dosage, therapeutic use)
• Carcinoma, Non-Small-Cell Lung (radiotherapy)
• Dose-Response Relationship, Radiation
• Drug Evaluation, Preclinical
• Humans
• Iodine Radioisotopes (administration & dosage, therapeutic use)
• Lung Neoplasms
• Membrane Proteins (immunology)
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Radioimmunotherapy (methods, standards)
• Transplantation, Heterologous
• Treatment Outcome