Pattern of antigen expression in metastases after radioimmunotherapy of a syngeneic rat colon carcinoma utilizing the BR96 antibody

30 of the 35 Brown Norway rats with syngeneic colon carcinoma treated with 400 MBq/kg 177Lu-DOTA-BR96 exhibited consistent complete response of the primary tumor. 13 animals developed metastases that were detected after treatment. The antigen expression was reduced in 17 of 23 metastases detected after radioimmunotherapy compared with untreated tumors. No tumors completely lacked positively stained tumor cells.Although it was not possible to demonstrate that the antigen reduction is triggered by the radioimmunotherapy this result stress the importance of considering the risk of reduced antigen expression in metastases after radioimmunotherapy prior to further targeted therapies.Treatment of primary tumors is often successful compared to that of metastatic disease, which is responsible for 90% of cancer mortality [1]. Radioimmunotherapy, the use of radiolabeled antibodies to localize radiation to the tumor, is considered a suitable treatment modality for smaller metastases [2]. Repeated administrations of radioimmunoconjugate may be required and/or beneficial in order to reduce toxicity and improve the outcome [3].The aim of the present study was to compare the antigen expression and distribution in metastases, detected after consistent complete response (CR) of the primary tumor following radioimmunotherapy with 177Lu-DOTA-BR96, to that of untreated primary tumors in a syngeneic immunocompetent rat colon carcinoma model.BR96 is a monoclonal antibody which binds to the Lewis Y antigen (Ley). Conjugation with the DOTA-chelate (S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid; Macrocyclics, Dallas, TX) and subsequent radiolabeling with 177LuCl3 solution (MDS Nordion, Vancouver, Canada) was performed according to Eriksson et al. [4]. The radiochemical purity of 177Lu-DOTA-BR96 was analyzed using ITLC and found to be >97.5%. Less than 1.3% labeled aggregated fractions was detected with HPLC.Brown Norway (BN) rats were used (Harlan, Horst, Neth