Pretargeting of prostate cancer with an internalizing anti-EGP-1 x anti-HSG bispecific antibody

1680 Objectives The monoclonal antibody RS7 (anti-EGP-1) effectively targets prostate cancer (PC), and because it internalizes, 111In-RS7 provides good tumor uptake. This study examined the prospects for using an anti-EGP-1 x anti-HSG bispecific antibody (bsMAb), TF12, for pretargeting. Methods Internalization of the anti-EGP1 antibody, RS7, and the bsMAb, TF12, by PC3 cells was determined in vitro in the presence or absence of di-HSG peptide (IMP288). Mice with s.c. human PC3 tumors were given 111In-TF12 and 125I-TF12 and necropsied 16 h later, while other mice were given 111In-IMP288 after the TF12 injection and then necropsied at 1, 2, 4, 24, 48, and 72 h p.i. Results RS7 and TF12 internalized at a comparable rate over 24 h, with evidence of early enhanced internalization in the presence of IMP288 (Table 1). 111In-TF12 uptake in PC3 cells was 7-fold higher than 125I-TF12 (4.9±0.6% ID/g vs. 0.7±0.2 %ID/g, respectively), indicating internalization also occurs in vivo. Nevertheless, TF12-pretargeted 111In-IMP288 uptake in the tumor was still high at 48 h after injection (50% of the %ID/g at 1 h). Conclusions Even though TF12 internalizes, it was highly effective for pretargeting prostate cancer. Due to the internalizing properties of the antibody, the radiolabel shows excellent retention in the tumor