Determination of chemotherapeutic activity in vivo by luminescent imaging of luciferase-transfected human tumors.

Abstract

Human DU-145 prostate and MCF-7 breast tumor cell lines were stably transfected with plasmid pcDNA3.1-Luc expressing firefly luciferase. Studies were performed with the transfected cell lines to evaluate luminescent imaging for measuring the efficacy of anti-cancer agents. In vitro experiments demonstrated a dose response of both cell lines to topotecan (Hycamtin) with an IC50 of 0.013 microM for MCF-7 Luc cells and 0.002 microM for DU-145 Luc cells. In vivo imaging experiments were performed using athymic nude mice inoculated i.p. with 5 x 10(6) MCF-7 cells or s.c. with 5 x 10(6) DU-145 cells and then treated with topotecan at 2.5 mg/kg body weight. Tumor progression and regression were monitored for 27 days. Animals inoculated s.c. with DU-145 Luc cells and then treated with topotecan demonstrated significant tumor growth and regression as measured with calipers and luminescent imaging. High correlation was observed between caliper and imaging results. The correlation coefficient was 0.75 for the control untreated group and 0.93 for the topotecan-treated group. Similarly, tumor progression and regression were measurable using luminescent imaging for untreated and topotecan-treated mice inoculated i.p. with MCF-7 Luc cells. These data indicate that luminescent imaging is a useful tool for evaluating anti-cancer drugs in vivo and may prove to be particularly useful for the development of novel agents. Luminescent imaging could also be used to locate and harvest residual tumors in drug-treated animals in order to study mechanisms of drug resistance.