Imaging primary lung cancers in mice to study radiation biology.
OBJECTIVE
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
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.
Kirsch
David G
DG
The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA. david.kirsch@duke.edu
Grimm
Jan
J
Guimaraes
Alexander R
AR
Wojtkiewicz
Gregory R
GR
Perez
Bradford A
BA
Santiago
Philip M
PM
Anthony
Nikolas K
NK
Forbes
Thomas
T
Doppke
Karen
K
Weissleder
Ralph
R
Jacks
Tyler
T
D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy; D016158:Genes, p53 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D023421:Models, Animal; D011853:Radiobiology; D012119:Respiration; D016896:Treatment Outcome; D047368:Tumor Burden; D055114:X-Ray Microtomography / Q000379:methods*