Dual-energy Micro-Computed Tomography Imaging of Radiation-Induced Vascular Changes in Primary Mouse Sarcomas

Int J Radiat Oncol Biol Phys. 2013 Apr 1;85(5):1353-9. doi: 10.1016/j.ijrobp.2012.09.027. Epub 2012 Nov 1.

Abstract

Purpose: To evaluate the effects of radiation therapy on primary tumor vasculature using dual-energy (DE) micro-computed tomography (micro-CT).

Methods and materials: Primary sarcomas were generated with mutant Kras and p53. Unirradiated tumors were compared with tumors irradiated with 20 Gy. A liposomal-iodinated contrast agent was administered 1 day after treatment, and mice were imaged immediately after injection (day 1) and 3 days later (day 4) with DE micro-CT. CT-derived tumor sizes were used to assess tumor growth. After DE decomposition, iodine maps were used to assess tumor fractional blood volume (FBV) at day 1 and tumor vascular permeability at day 4. For comparison, tumor vascularity and vascular permeability were also evaluated histologically by use of CD31 immunofluorescence and fluorescently-labeled dextrans.

Results: Radiation treatment significantly decreased tumor growth from day 1 to day 4 (P<.05). There was a positive correlation between CT measurement of tumor FBV on day 1 and extravasated iodine on day 4 with microvascular density (MVD) on day 4 (R(2)=0.53) and dextran accumulation (R(2)=0.63) on day 4, respectively. Despite no change in MVD measured by histology, tumor FBV significantly increased after irradiation as measured by DE micro-CT (0.070 vs 0.091, P<.05). Both dextran and liposomal-iodine accumulation in tumors increased significantly after irradiation, with dextran fractional area increasing 5.2-fold and liposomal-iodine concentration increasing 4.0-fold.

Conclusions: DE micro-CT is an effective tool for noninvasive assessment of vascular changes in primary tumors. Tumor blood volume and vascular permeability increased after a single therapeutic dose of radiation treatment.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blood Volume / physiology
  • Blood Volume / radiation effects*
  • Capillary Permeability / physiology
  • Capillary Permeability / radiation effects*
  • Contrast Media
  • Fluorescent Antibody Technique / methods
  • Iodine
  • Liposomes / administration & dosage
  • Mice
  • Nanoparticles / administration & dosage
  • Perfusion Imaging / methods
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Radiation Dosage
  • Sarcoma / blood supply*
  • Sarcoma / pathology
  • Sarcoma / radiotherapy*
  • Tumor Burden
  • X-Ray Microtomography / methods*

Substances

  • Contrast Media
  • Liposomes
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Iodine