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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.

Dual-energy micro-computed tomography imaging of radiation-induced vascular changes in primary mouse sarcomas.

Author information

1
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA.

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.

PMID:
23122984
PMCID:
PMC3625949
DOI:
10.1016/j.ijrobp.2012.09.027
[Indexed for MEDLINE]
Free PMC Article

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