Imaging Primary Lung Cancers in Mice to Study Radiation Biology
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.
∗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
§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
∗∗Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA
††Department of Radiology, Massachusetts General Hospital, Boston, MA
‡‡Howard Hughes Medical Institute, Chevy Chase, MD
Reprint requests to: David G. Kirsch, Box 91006, Duke University Medical Center, Durham, NC 27708. Tel: (919) 681-8586; Fax: (919) 681-1867
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.
ABSTRACT