Imaging Primary Lung Cancers in Mice to Study Radiation Biology

Grimm, Jan; Guimaraes, Alexander R; Wojtkiewicz, Gregory R; Perez, Bradford A; Santiago, Philip M; Anthony, Nikolas K; Forbes, Thomas; Doppke, Karen

doi:10.1016/j.ijrobp.2009.11.038

Title: Imaging Primary Lung Cancers in Mice to Study Radiation Biology

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Abstract

Purpose: To image a genetically engineered mouse model of non-small-cell lung cancer with micro-computed tomography (micro-CT) to measure tumor response to radiation therapy. Methods and Materials: The Cre-loxP system was used to generate primary lung cancers in mice with mutation in K-ras alone or in combination with p53 mutation. Mice were serially imaged by micro-CT, and tumor volumes were determined. A comparison of tumor volume by micro-CT and tumor histology was performed. Tumor response to radiation therapy (15.5 Gy) was assessed with micro-CT. Results: The tumor volume measured with free-breathing micro-CT scans was greater than the volume calculated by histology. Nevertheless, this imaging approach demonstrated that lung cancers with mutant p53 grew more rapidly than lung tumors with wild-type p53 and also showed that radiation therapy increased the doubling time of p53 mutant lung cancers fivefold. Conclusions: Micro-CT is an effective tool to noninvasively measure the growth of primary lung cancers in genetically engineered mice and assess tumor response to radiation therapy. This imaging approach will be useful to study the radiation biology of lung cancer.

Authors:

Grimm, Jan ^[1]; Guimaraes, Alexander R ^[1]; Wojtkiewicz, Gregory R ^[1]; Perez, Bradford A ^[2]; Santiago, Philip M ^[3]; Anthony, Nikolas K; Forbes, Thomas; Doppke, Karen ^[4]

Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA (United States)
Departments of Radiation Oncology and Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC (United States)
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA (United States)
Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States)

Publication Date:: Mon Mar 15 00:00:00 EDT 2010

OSTI Identifier:: 21372148

Resource Type:: Journal Article

Journal Name:: International Journal of Radiation Oncology, Biology and Physics

Additional Journal Information:: Journal Volume: 76; Journal Issue: 4; Other Information: DOI: 10.1016/j.ijrobp.2009.11.038; PII: S0360-3016(09)03604-9; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Journal ID: ISSN 0360-3016

Country of Publication:: United States

Language:: English

Subject:: 62 RADIOLOGY AND NUCLEAR MEDICINE; CAT SCANNING; GROWTH; HISTOLOGY; IMAGES; LUNGS; MICE; MUTANTS; NEOPLASMS; RADIOBIOLOGY; RADIOTHERAPY; ANIMALS; BIOLOGY; BODY; COMPUTERIZED TOMOGRAPHY; DIAGNOSTIC TECHNIQUES; DISEASES; MAMMALS; MEDICINE; NUCLEAR MEDICINE; ORGANS; RADIOLOGY; RESPIRATORY SYSTEM; RODENTS; THERAPY; TOMOGRAPHY; VERTEBRATES

Citation Formats


                    Kirsch, David G., E-mail: david.kirsch@duke.ed, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, Departments of Radiation Oncology and Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, Grimm, Jan, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York, NY, Guimaraes, Alexander R, Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, Department of Radiology, Massachusetts General Hospital, Boston, MA, Wojtkiewicz, Gregory R, Perez, Bradford A, Santiago, Philip M, Anthony, Nikolas K, Forbes, Thomas, and Doppke, Karen. Imaging Primary Lung Cancers in Mice to Study Radiation Biology.  United States: N. p., 2010. 
        Web.  doi:10.1016/j.ijrobp.2009.11.038.

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                    Kirsch, David G., E-mail: david.kirsch@duke.ed, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, Departments of Radiation Oncology and Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, Grimm, Jan, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York, NY, Guimaraes, Alexander R, Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, Department of Radiology, Massachusetts General Hospital, Boston, MA, Wojtkiewicz, Gregory R, Perez, Bradford A, Santiago, Philip M, Anthony, Nikolas K, Forbes, Thomas, & Doppke, Karen. Imaging Primary Lung Cancers in Mice to Study Radiation Biology.  United States.  https://doi.org/10.1016/j.ijrobp.2009.11.038

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                    Kirsch, David G., E-mail: david.kirsch@duke.ed, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, Departments of Radiation Oncology and Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, Grimm, Jan, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York, NY, Guimaraes, Alexander R, Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, Department of Radiology, Massachusetts General Hospital, Boston, MA, Wojtkiewicz, Gregory R, Perez, Bradford A, Santiago, Philip M, Anthony, Nikolas K, Forbes, Thomas, and Doppke, Karen. 2010.  
        "Imaging Primary Lung Cancers in Mice to Study Radiation Biology".  United States.  https://doi.org/10.1016/j.ijrobp.2009.11.038.

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@article{osti_21372148,

  title        = {Imaging Primary Lung Cancers in Mice to Study Radiation Biology},

  author       = {Kirsch, David G., E-mail: david.kirsch@duke.ed and Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA and Departments of Radiation Oncology and Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC and Grimm, Jan and Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY and Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York, NY and Guimaraes, Alexander R and Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA and Department of Radiology, Massachusetts General Hospital, Boston, MA and Wojtkiewicz, Gregory R and Perez, Bradford A and Santiago, Philip M and Anthony, Nikolas K and Forbes, Thomas and Doppke, Karen},

  abstractNote = {Purpose: To image a genetically engineered mouse model of non-small-cell lung cancer with micro-computed tomography (micro-CT) to measure tumor response to radiation therapy. Methods and Materials: The Cre-loxP system was used to generate primary lung cancers in mice with mutation in K-ras alone or in combination with p53 mutation. Mice were serially imaged by micro-CT, and tumor volumes were determined. A comparison of tumor volume by micro-CT and tumor histology was performed. Tumor response to radiation therapy (15.5 Gy) was assessed with micro-CT. Results: The tumor volume measured with free-breathing micro-CT scans was greater than the volume calculated by histology. Nevertheless, this imaging approach demonstrated that lung cancers with mutant p53 grew more rapidly than lung tumors with wild-type p53 and also showed that radiation therapy increased the doubling time of p53 mutant lung cancers fivefold. Conclusions: Micro-CT is an effective tool to noninvasively measure the growth of primary lung cancers in genetically engineered mice and assess tumor response to radiation therapy. This imaging approach will be useful to study the radiation biology of lung cancer.},

  doi          = {10.1016/j.ijrobp.2009.11.038},

  url          = {https://www.osti.gov/biblio/21372148},
  journal      = {International Journal of Radiation Oncology, Biology and Physics},

  issn         = {0360-3016},

  number       = 4,

  volume       = 76,

  place        = {United States},

  year         = {Mon Mar 15 00:00:00 EDT 2010},

  month        = {Mon Mar 15 00:00:00 EDT 2010}

}

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