When cancers progress, many of them spread throughout the body and give rise to cancerous tissue far away from the original tumour. This process is termed ‘metastasis’ and is responsible for >90% of human cancer deaths. To gain better insight into the molecular processes underlying cancer progression and metastasis, it would be highly beneficial to non-invasively visualize the primary tumour and derived metastases in animal models. These models could then also be used to investigate the efficacy of new drugs and treatment concepts, in particular for the development of therapies intended to interfere with cancer spread.
(1) We engineer cancer models to render them in vivo traceable.
This spans human cancer models as well as rodent ones, and our approaches are suitable to track cancer progression in xenograft as well as fully immunocompetent (rodent) settings. We generated several traceable models across different cancer types including breast cancer, skin cancer, liver cancer, and lately also lung cancer.
We frequently adopt a so-called multi-modal multi-scale approach, which means that we combine different imaging types that complement one another for the purpose of obtaining information across multiple length scales (molecules ↔ cells ↔ organs ↔ whole-body). This also allows us to correlate the information from non-invasive whole-body imaging with parameters accessible from harvested tissues .
A mouse with an in vivo traceable triple negative breast cancer expressing a dual-mode radionuclide-fluorescence reporter. (Left) PET/CT image; 3D rendering and maximum intensity projection with yellow areas indicating cancerous tissues. (Middle) Segmentation of individual cancerous tissues and quantificatino of radiactivity in these tissues. (Right) Harvested lung tissues as viewed in daylight and under blacklight during tissue dissection and immunofluorescence microscopy of a tissue section from the primary tumour (indicating individual cancer cells as ‘green rings’, blood vessels (red) and cell nuclei (blue). More…
(2) We use in vivo traceable cancer models to study the effects of new and experimental treatments on cancer progression and metastasis.
For example, we have already employed such in vivo traceable cancer models to investigate the effects of chemotherapies and immunotherapies on tumour growth and metastasis. Recently, we also suggested a preclinical pipeline approach for the identification and validation of new drugs intended to interfere with melanoma cell spread.
In other projects, we are employing such in vivo traceable cancer models to evaluate the impact of certain radioisotopes on cancer. This includes safety evaluations for certain medical imaging isotopes (e.g. the SPECT isotope Tc-99m) as well as comparisons of various radioisotopes with potential for molecular radiotherapy.