title: Treatment with unlabeled mAb BR96 after radioimmunotherapy with 177Lu-DOTA-BR96 in a syngeneic rat colon carcinoma model.
abstract: Metastatic disease after successful treatment of the primary tumor continues to be a therapeutic challenge. Enhancement of therapeutic effects by the administration of unlabeled monoclonal antibodies (mAbs) after radioimmunotherapy (RIT) may provide a means of preventing or delaying the development of metastatic disease. In the present study, Brown Norway rats with syngeneic grafted colon carcinomas were administered the minimal effective therapeutic dose of 400 MBq/kg lutetium-177 ((177)Lu)-DOTA-BR96. After 2 weeks, half of the animals were given 15 mg/kg unlabeled mAb BR96 as consolidation therapy. Treatment response and toxicity were monitored 100 days after the treatment with unlabeled BR96. The treatment with unlabeled mAb after RIT resulted in a complete response (CR) in 19 of 19 animals, while RIT alone resulted in a CR in 17 of 19 animals. The additional treatment did not affect the number of animals with metastatic disease or the time to clinical symptoms of metastases. RIT resulted in reversible myelotoxicity. The unlabeled mAb BR96 did not cause any additional toxicity, making it possible to repeat the consolidation therapy.
authors.affiliation: Department of Oncology, Lund University, Sweden. sophie.eriksson@med.lu.se
authors.forename: Sophie E
authors.initials: SE
authors.lastname: Eriksson
authors.forename: Tomas
authors.initials: T
authors.lastname: Ohlsson
authors.forename: Rune
authors.initials: R
authors.lastname: Nilsson
authors.forename: Jan
authors.initials: J
authors.lastname: Tennvall
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002614:Chelating Agents / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006573:Heterocyclic Compounds, 1-Ring / Q000627:therapeutic use; D007124:Immunoenzyme Techniques; D008187:Lutetium / Q000627:therapeutic use; D008297:Male; D016499:Radioimmunotherapy; D011868:Radioisotopes / Q000627:therapeutic use; D051381:Rats; D011914:Rats, Inbred BN
chemical_list: D000911:Antibodies, Monoclonal; C507851:BR96 monoclonal antibody; D002614:Chelating Agents; D006573:Heterocyclic Compounds, 1-Ring; D011868:Radioisotopes; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D008187:Lutetium