EVALUATION OF PREIRRADATION ON MONOCLONAL-ANTIBODY LOCALIZATION IN COLON-TUMOR XENOGRAFTS EXPRESSING A CELL-ASSOCIATED ANTIGEN

We have previously demonstrated that external beam irradiation can inc rease radiolabeled monoclonal antibody (MAb) targeting of tumors expre ssing carcinoembryonic antigen (CEA), a secreted glycoprotein, Increas ed tumor uptake was seen with both protons and gamma radiation (Co-60) . However, although pre-irradiation with protons resulted in greater a ctivity within tumors than conventional radiation, normal tissues also exhibited increased uptake. This suggested that proton beam irradiati on allowed more CEA to escape and bind to radiolabeled MAb in sites ot her than tumor. The purpose of the present study was to determine if a similar effect could be achieved, but without an increase in normal t issue activity, with a MAb directed against a cell-bound antigen. T380 and LS174T human colon tumors were implanted s.c. into athymic nude m ice and irradiated with 10 Gy Co-60 or proton beam. In-111-CYT-103 MAb (anti-TAG-72) was injected i.p. 2 hr later and the biodistribution of activity was determined 2 days thereafter. Tumor size at the time of external beam irradiation and biodistribution studies was similar amon g the groups within each tumor type. Increased targeting of radiolabel ed MAb within tumors was not observed in either model after external b eam irradiation compared to their respective nonirradiated controls, a lthough some differences were observed in normal tissue uptake. These findings demonstrate that preirradiation for the purpose of enhancing MAb delivery to the tumor site is nor a universal phenomenon and may b e successful only with certain antibody/tumor antigen systems.