Sequential radioimmunotherapy with 177Lu- and 211At-labeled monoclonal antibody BR96 in a syngeneic rat colon carcinoma model.

Abstract

UNLABELLED:

Alpha-particle emitters, such as astatine-211 (211At), are generally considered suitable for the treatment of small cell clusters due to their short path length, while beta-particle emitters, for example, Lutetium-177 (177Lu), have a longer path length and are considered better for small, established tumors. A combination of such radionuclides may be successful in regimens of radioimmunotherapy. In this study, rats were treated by sequential administration of first a 177Lu-labeled antibody, followed by a 211At-labeled antibody 25 days later.

METHODS:

Rats bearing solid colon carcinoma tumors were treated with 400 MBq/kg body weight 177Lu-BR96. After 25 days, three groups of animals were given either 5 or 10 MBq/kg body weight of 211At-BR96 simultaneously with or without a blocking agent reducing halogen uptake in normal tissues. Control animals were not given any 211At-BR96. Myelotoxicity, body weight, tumor size, and development of metastases were monitored for 120 days.

RESULTS:

Tumors were undetectable in 90% of the animals on day 25, independent of treatment. Additional treatment with 211At-labeled antibodies did not reduce the proportion of animals developing metastases. The rats suffered from reversible myelotoxicity after treatment.

CONCLUSIONS:

Sequential administration of 177Lu-BR96 and 211At-BR96 resulted in tolerable toxicity providing halogen blocking but did not enhance the therapeutic effect.

• Authors: Sophie E Eriksson, Erika Elgström, Tom Bäck, Tomas Ohlsson, Holger Jensen, Rune Nilsson, Sture Lindegren, Jan Tennvall
• Journal: Cancer biotherapy & radiopharmaceuticals (Cancer Biother Radiopharm) Vol. 29 Issue 6 Pg. 238-46 (Aug 2014) ISSN: 1557-8852 [Electronic] United States
• PMID: 24971673 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• BR96 monoclonal antibody
• Radioisotopes
• Radiopharmaceuticals
• Lutetium
• Astatine

Topics

• Alpha Particles
• Animals
• Antibodies, Monoclonal (administration & dosage, immunology)
• Astatine (administration & dosage)
• Colonic Neoplasms (immunology, pathology, radiotherapy)
• Disease Models, Animal
• Humans
• Lutetium (administration & dosage)
• Radioimmunotherapy (methods)
• Radioisotopes (administration & dosage)
• Radiopharmaceuticals (administration & dosage)
• Rats