25 Citations (Scopus)

Abstract

The purpose of this study was to develop a rat orthotopic lung tumor model with a solitary intrapulmonary nodule to study the effects of high-dose radiation. A549-Luc non-small cell lung cancer (NSCLC) cells were implanted into nude rats in the intercostal space between ribs 5 and 6 of the rig t lung. Bioluminescence and microcomputed tomography (CT) imaging were performed after implantation to confirm the presence of a solitary tumor and to monitor tumor growth. A device using image guidance for localization was developed to facilitate high-precision irradiation in small animals. A pilot irradiation study was performed, and response was assessed by bioluminescence imaging and immunohistochemistry. Radiation response was confirmed through serial bioluminescence imaging, and the strength of the bioluminescence signal was observed to be inversely proportional to dose. Response was also observed by the monoclonal antibody bavituximab, which binds to exposed lipid phosphatidylserine (PS) on tumor vessels. The ability to (1) reproducibly generate solitary tumor nodules in the rat lung, (2) identify and monitor tumor growth by bioluminescence imaging and CT imaging, (3) accurately target these tumors using high doses of radiation, and (4) demonstrate and quantify radiation response using bioluminescence imaging provides significant opportunity to probe the biological mechanisms of high-dose irradiation in preclinical settings.

Original languageEnglish (US)
Pages (from-to)62-71
Number of pages10
JournalRadiation Research
Volume174
Issue number1
DOIs
StatePublished - Jul 2010

Fingerprint

bioluminescence
lungs
rats
tumors
Lung
Neoplasms
Radiation
dosage
nodules
radiation
irradiation
Nude Rats
X-Ray Microtomography
Phosphatidylserines
Ribs
Growth
antibodies
Non-Small Cell Lung Carcinoma
vessels
animals

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Biophysics
  • Radiation

Cite this

An orthotopic lung tumor model for image-guided microirradiation in rats. / Saha, Debabrata; Watkins, Linda; Yin, Yi; Thorpe, Philip; Story, Michael D.; Song, Kwang; Raghavan, Pavithra; Timmerman, Robert; Chen, Benjamin; Minna, John D.; Solberg, Timothy D.

In: Radiation Research, Vol. 174, No. 1, 07.2010, p. 62-71.

Research output: Contribution to journalArticle

Saha, Debabrata ; Watkins, Linda ; Yin, Yi ; Thorpe, Philip ; Story, Michael D. ; Song, Kwang ; Raghavan, Pavithra ; Timmerman, Robert ; Chen, Benjamin ; Minna, John D. ; Solberg, Timothy D. / An orthotopic lung tumor model for image-guided microirradiation in rats. In: Radiation Research. 2010 ; Vol. 174, No. 1. pp. 62-71.
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AU - Raghavan, Pavithra

AU - Timmerman, Robert

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