Transfer to Increase Uptake of Radiolabeled Iododeoxyuridine in a Murine Model

In vitro and in vivo experiments from our laboratory and others have suggested that the combination of thymidylate synthase (TS) inhibitor and radiolabeled iododeoxyuridine (IdUrd) is syn-ergistic. Efficacy is limited by drug resistance, which is often mediated by TS overexpression. We designed an in vivo elec-trogene transfer (EGT) model for delivering antisense TS plas-mid (ATS) into tumor to increase the subsequent efficacy of 131I-IdUrd therapy. Methods: Plasmid complementary to nucle-otide 531-710 in the coding region of the mouse TS (mTS) mRNA was constructed. TS activity and 131I-IdUrd DNA incor-poration were determined 48 h after in vitro EGT of ATS to CT26 cells. In vivo therapeutic effect and radioactivity retained in tumor after various combinations of EGT ATS, 5-fluorouracil (5-FU), and continuous infusion of 131I-IdUrd by osmotic minipump were determined. Results: A reduction of TS activit