New technologies are needed to detect tumours at early stages and also to non-invasively monitor tumour progression or the response to therapy. Ralph Weissleder and colleagues have created an in vivo molecular imaging method to identify and track lung tumours in mice, which might eventually be developed to do the same in patients.

Through gene-expression-profiling analysis, Weissleder's group, with colleagues in Tyler Jack's laboratory, found that cathepsin cysteine proteases are overexpressed in a mouse model of lung adenocarcinoma. In this model, lung tumorigenesis is induced by the overexpression of KRAS specifically in the respiratory epithelia, and the resulting adenocarcinomas resemble human tumours at the molecular and histological level. Using an optical probe that is selectively activated by cathepsin proteases and a new tomograghic imaging modality, the authors were able to detect lung tumours as small as 1 mm in diameter in live mice (see figure). Three-dimensional maps of the fluorescence signal, fused with computed tomography images, showed a close correlation between fluorescence signal and tumour burden. Importantly, the group was able to follow tumour progression over time by serial imaging of the same mouse.

Cathepsin proteases are also overexpressed by human lung adenocarcinomas, as well as colorectal cancers, pancreatic adenocarcinoma and oral squamous cell carcinoma. So, this technology might eventually be developed to identify various types of tumours and to track their progression in patients.