Use of gene expression profiling to direct in vivo molecular imaging of lung cancer.
Using gene expression profiling, we identified cathepsin cysteine proteases as highly up-regulated genes in a mouse model of human lung adenocarcinoma. Overexpression of cathepsin proteases in these lung tumors was confirmed by immunohistochemistry and Western blotting. Therefore, an optical probe activated by cathepsin proteases was selected to detect murine lung tumors in vivo as small as 1 mm in diameter and spatially separated. We generated 3D maps of the fluorescence signal and fused them with anatomical computed tomography images to show a close correlation between fluorescence signal and tumor burden. By serially imaging the same mouse, optical imaging was used to follow tumor progression. This study demonstrates the capability for molecular imaging of a primary lung tumor by using endogenous proteases expressed by a tumor. It also highlights the feasibility of using gene expression profiling to identify molecular targets for imaging lung cancer.
Grimm
Jan
J
Center for Molecular Imaging Research and Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Kirsch
David G
DG
Windsor
Stephen D
SD
Kim
Carla F Bender
CF
Santiago
Philip M
PM
Ntziachristos
Vasilis
V
Jacks
Tyler
T
Weissleder
Ralph
R
D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000175:diagnosis*; D000818:Animals; D015153:Blotting, Western; D002403:Cathepsins / Q000235:genetics / Q000378:metabolism*; D003952:Diagnostic Imaging / Q000379:methods*; D005453:Fluorescence; D020869:Gene Expression Profiling / Q000379:methods*; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000175:diagnosis*; D051379:Mice; D008817:Mice, Mutant Strains; D041622:Tomography, Optical / Q000379:methods; D015854:Up-Regulation
D002403:Cathepsins