Use of gene expression profiling to direct in vivo molecular imaging of lung cancer

Abstract

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.

Mouse Models of Human Non-Small-Cell Lung Cancer: Raising the Bar

“…Using a micro-CT with a voxel resolution of 72 microns, K-ras LSL lung tumors can be detected with sub-millimeter resolution (Grimm et al 2005). Images collected after AdCre infection have led to several interesting observations.…”

“…Three-dimensional maps of the fluorescence signal fused with anatomical CT images showed a close correlation between fluorescence signal and tumor burden (Fig. 2) (Grimm et al 2005). Cathepsin proteases are also overexpressed in some patients with lung cancer, and their expression has been associated with tumor invasion and poor prognosis (Schweiger et al 2000;Joyce et al 2004).…”

The use of fluorescent dyes and probes in surgical oncology

“…54 The tumoral protease activity was used to improve the detection of small peripheral lung cancer in the Lewis Lung Carcinoma model by use of a novel ProSense 750. 55 In this study, the imaging was performed by NIR microcatheters during thoracoscopy.…”

“…Three probes have been designed so far by one research group and they are all activated by protease Cathepsin B. [51][52][53][54][55][56] This protease is known to be up-regulated in areas of inflammation, necrosis, angiogenesis and focal invasion. 57 Being optically silent when injected, the probes have a low background signal which results in higher signal-to-background ratios when compared to nonspecific probes.…”

Molecular MR Imaging of Cancer Gene Therapy: Ferritin Transgene Reporter Takes the Stage

“…In fact, the coupling of molecular imaging with recent advances in``-omics'' research, such as genomics and proteomics studies, evidences the promise of these approaches to revolutionize the diagnostic imaging of cancer. 2 Molecular imaging utilizes various imaging modalities, the 3 major methods being optical imaging, MR imaging, and nuclear medicine modalities, such as positron emission tomography (PET) and single photon emission computed tomography (SPECT). The advantages and disadvantages of each modality have been discussed elsewhere.…”