title: An orthotopic lung tumor model for image-guided microirradiation in rats.
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 right 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.
authors.affiliation: Department of Radiation Oncology, Division of Molecular Radiation Biology and Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, Texas 75390-9187, USA.
authors.forename: Debabrata
authors.initials: D
authors.lastname: Saha
authors.forename: Linda
authors.initials: L
authors.lastname: Watkins
authors.forename: Yi
authors.initials: Y
authors.lastname: Yin
authors.forename: Philip
authors.initials: P
authors.lastname: Thorpe
authors.forename: Michael D
authors.initials: MD
authors.lastname: Story
authors.forename: Kwang
authors.initials: K
authors.lastname: Song
authors.forename: Pavithra
authors.initials: P
authors.lastname: Raghavan
authors.forename: Robert
authors.initials: R
authors.lastname: Timmerman
authors.forename: Benjamin
authors.initials: B
authors.lastname: Chen
authors.forename: John D
authors.initials: JD
authors.lastname: Minna
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Solberg
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D049449:Luminescence; D008175:Lung Neoplasms / Q000473:pathology*; D009368:Neoplasm Transplantation; D051381:Rats; D011923:Rats, Nude; D014057:Tomography, X-Ray Computed