International Journal of Radiation Oncology * Biology * Physics
Volume 76, Issue 4 , Pages 973-977, 15 March 2010

Imaging Primary Lung Cancers in Mice to Study Radiation Biology

  • David G. Kirsch, M.D., Ph.D.

      Affiliations

    • The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA
    • Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA
    • Departments of Radiation Oncology and Pharmacology & Cancer Biology, Duke University Medical Center, Durham, NC
    • Corresponding Author InformationReprint requests to: David G. Kirsch, Box 91006, Duke University Medical Center, Durham, NC 27708. Tel: (919) 681-8586; Fax: (919) 681-1867
  • ,
  • Jan Grimm, M.D.

      Affiliations

    • Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA
    • Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY
    • Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York, NY
  • ,
  • Alexander R. Guimaraes, M.D., Ph.D.

      Affiliations

    • Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA
    • Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA
    • Department of Radiology, Massachusetts General Hospital, Boston, MA
  • ,
  • Gregory R. Wojtkiewicz, M.S.

      Affiliations

    • Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA
  • ,
  • Bradford A. Perez, B.S.

      Affiliations

    • Departments of Radiation Oncology and Pharmacology & Cancer Biology, Duke University Medical Center, Durham, NC
  • ,
  • Philip M. Santiago, B.S.

      Affiliations

    • The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA
  • ,
  • Nikolas K. Anthony, R.T.T.

      Affiliations

    • Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA
  • ,
  • Thomas Forbes, R.T.T.

      Affiliations

    • Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA
  • ,
  • Karen Doppke, M.S.

      Affiliations

    • Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA
  • ,
  • Ralph Weissleder, M.D., Ph.D.

      Affiliations

    • Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA
    • Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA
    • Department of Radiology, Massachusetts General Hospital, Boston, MA
  • ,
  • Tyler Jacks, Ph.D.

      Affiliations

    • The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA
    • Howard Hughes Medical Institute, Chevy Chase, MD

Received 8 September 2009; received in revised form 10 November 2009; accepted 10 November 2009.

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.

Genetically engineered mouse models of cancer, Lung cancer, Micro–computed tomography, K-Ras, p53

To access this article, please choose from the options below

Login to an existing account or Register a new account.

  • Purchase this article for 30.00 USD (You must login/register to purchase this article)

    Online access for 24 hours. The PDF version can be downloaded as your permanent record.

  • Subscribe to this title

    Get unlimited online access to this article and all other articles in this title 24/7 for one year.

  • Claim access now

    For current subscribers with Society Membership or Account Number.

  • Visit SciVerse ScienceDirect to see if you have access via your institution.
 

 Supported by the Howard Hughes Medical Institute (T.J., B.A.P.), American Cancer Society Institutional Research Grant, KO8 CA 114176 (D.G.K.), P50 CA86355 (D.G.K., R.W.), R24 CA92782 (R.W.), U24 CA 092782 (R.W., T.J.), NCI grant 5-U01-CA84306 (T.J.), partially by Cancer Center Support (core) grant P30-CA14051 from the NCI (T.J.) and by a medical student seed grant from the RSNA (B.A.P.). Dr. Jacks is the David H. Koch Professor of Biology and a Daniel K. Ludwig Scholar.

 Conflict of interest: none.

PII: S0360-3016(09)03604-9

doi:10.1016/j.ijrobp.2009.11.038

International Journal of Radiation Oncology * Biology * Physics
Volume 76, Issue 4 , Pages 973-977, 15 March 2010