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

Nanomedicine. 2018 Jan;14(1):27-34. doi: 10.1016/j.nano.2017.08.013. Epub 2017 Sep 4.

Abstract

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.

Keywords: Hypoxia; Liposome; PET; Radio-sensitizer; Radiotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colorectal Neoplasms / diagnostic imaging
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / radiotherapy
  • Copper Radioisotopes / administration & dosage
  • Copper Radioisotopes / pharmacokinetics
  • Female
  • Gamma Rays / therapeutic use*
  • Head and Neck Neoplasms / diagnostic imaging
  • Head and Neck Neoplasms / metabolism*
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / radiotherapy
  • Humans
  • Hypoxia / metabolism
  • Liposomes / administration & dosage
  • Liposomes / pharmacokinetics*
  • Mice
  • Mice, Nude
  • Positron Emission Tomography Computed Tomography / methods
  • Radiation Dosage
  • Tissue Distribution
  • Treatment Outcome
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Copper Radioisotopes
  • Liposomes