Differentiation of tumor sensitivity to photodynamic therapy and early evaluation of treatment effect by nuclear medicine techniques

Abstract

Our final goal is to develop an appropriate method using nuclear medicine technique for monitoring the effect and prediction of Photodynamic Therapy (PDT) on tumors. The aim of this study is to evaluate the effect of PDT on tumor cells in vitro using (18)F-FDG and (99m)Tc-MIBI as tracers. Five tumor cell lines (A431, DU145, H1650, LS180, SHIN3) with varied characteristics were irradiated after incubating for 24h with several doses of Photofrin (PF). Singlet oxygen was monitored by the near-IR emission detection system during irradiation and generated (1)O2 was calculated. PDT effects were rapidly evaluated by nuclear medicine techniques (uptake of (18)F-FDG and (99m)Tc-MIBI) and traditional methods for cell viability (MTT and trypan blue assays) at 3h after PDT. Intracellular PF concentration was measured by absorption spectrometer and cell protein content was measured by the Lowry method. (18)F-FDG uptake, (99m)Tc-MIBI uptake, singlet oxygen, and intracellular PF concentration were standardized by protein content. Decrease % of (18)F-FDG and (99m)Tc-MIBI, MTT, and trypan blue was normalized to the control group. Decrease % of (18)F-FDG was exponentially related to decrease % of MTT (R (2)=0.650, P<0.01) while decrease % of (99m)Tc-MIBI was linearly related to that of MTT (R (2)=0.719, P<0.01). The decrease % of MTT was more sensitive than that of trypan blue. However, neither (1)O2 nor PF uptake was correlated with sensitivity to PDT. In addition, (18)F-FDG uptake before PDT was linearly related to decrease % of MTT (R (2)=0.800, P<0.05). Our findings in in vitro studies suggest that (99m)Tc-MIBI is better than (18)F-FDG for early evaluation of PDT effect, but (18)F-FDG uptake may be used to predict PDT sensitivity before therapy.