Objectives: 

Functional imaging has become an important tool in oncology by informing about localization and size of the tumour as well as the pathophysiological features of tumoural cells. One of the most characteristic features of some tumour types is the activation of the neoangiogenic program which is specifically mediated by the transcription factor HIF-1alpha, an important player in regulating this process and a prognostic marker of tumoural aggressiveness. In previous reports, our group has developed and characterized a genetically encoded biosensor activatable by HIF-1alpha that permits the tumour follow-up by means of optical tracers. Our main goal is to validate our results obtained in vitro in a established model of metastasis.

Materials: 

In order to establish a murine model of metastasis we injected intravenously cells from the breast cancer cell line MDA MB-231 in BALB/c nude mice. Previously we have established several stable cell lines carrying our biosensor and assessed their fluorescence and bioluminescence performances in vitro. To validate the detection of tumoural mases by means of optical methods (fluorescence, bioluminescence) we have analyzed biochemically samples from these masses.

Results: 

Here we report a non-invasive in vivo detection of lung micrometastases in a mouse model of breast cancer using self-illuminating genetically encoded tracers responsive to intracellular HIF-1alpha levels and a preliminary analysis of the contribution of the tumoural masses to the metastatic niche. We have been succesful in detecting tumoural masses by means of fluorescence, bioluminescence and BRET (bioluminescence resonant energy transfer).

Conclusions: 

This model lays the foundations for novel hypoxia sensing probes able to detect micrometastatic disease with high sensitivity and specificity. Thus, optical functional imaging shows promise in the understanding of disease, drug development or image-guided therapy.