Liposome accumulation in irradiated tumors display important tumor and dose dependent differences

Radiation therapy may affect several important parameters in the tumor microenvironment and thereby influence the accumulation of liposomes by the enhanced permeability and retention (EPR)-effect. Here we investigate the effect of single dose radiation therapy on liposome tumor accumulation by PET/CT imaging using radiolabeled liposomes. Head and neck cancer xenografts (FaDu) and syngenic colorectal (CT26) cancer models were investigated. Radiotherapy displayed opposite effects in the two models. FaDu tumors displayed increased mean accumulation of liposomes for radiation doses up to 10 Gy, whereas CT26 tumors displayed a tendency for decreased accumulation. Tumor hypoxia was found negatively correlated to microregional distribution of liposomes. However, liposome distribution in relation to hypoxia was improved at lower radiation doses. The study reveals that the heterogeneity in liposome tumor accumulation between tumors and different radiation protocols are important factors that need to be taken into consideration to achieve optimal effect of liposome based radio-sensitizer therapy. The enhanced permeability and retention (EPR) effect serves as the basis for liposome accumulation within solid cancers. The EPR effect is, however, not a ubiquitous phenomenon and varies significantly between tumors. Radiation therapy affects both cancer cells directly and the tumor vasculature and microenvironment. Using PET imaging, radiation therapy was found to increase the accumulation of radiolabeled liposomes in head and neck xenograft model. Radiation therapy may improve EPR dependent delivery of liposomal chemotherapeutics to yield an improved tumor targeted therapeutic combination. [Display omitted]