The service project Z2 is conceived to develop and provide methods for in vivo imaging of tumor growth and metastasis as well as of developmental processes in mice. In the second funding period multiple projects have benefited from the visualization of processes such as neovascularization, tumor metabolism, high throughput tumor screening in murine models, and accumulation of immunosuppressive cells in the tumor microenvironment and metastatic spread of tumor cells in vivo. During the third funding period in vivo imaging by 2-photon microscopy (Lämmermann, project A3) mainly for detection of the interaction of migrating tumor cells with their environment will be established. This will provide in addition to the real time macroscopic information by MRI and BLI additional information on the microscopic level on the anatomical localization of cells and thereby extend the armamentarium of the animal imaging platform. Furthermore, in addition to in vivo bioluminescence imaging (BLI), animal MR and positron emission tomography (PET-CT), ultrasound has become available. Ultrasound (US) and BLI can be used to study inoculated cells in a high-throughput fashion and display small detected metastases in a three-dimensional anatomical context. Conversely, MRI offers a deeper insight into structure and function of solid tumors with respect to vessel architecture and anatomical localization. The different imaging techniques form a highly comprehensive and versatile imaging portfolio for future morphological, physiological, functional and molecular imaging studies. To facilitate the choice of the different imaging techniques, an imaging platform has been established that will support each project PI to decide for the most suitable technique to answer his/her biological question.
The main Goal of the Z2 US project is to provide non-invasive US imaging as a valuable and effective in vivo method that allows both the presentation of the processes of carcinogenesis and the investigation of the therapy response of tumors to all PIs of the SFB 850.
The major advantage of ultrasound screening compared to other imaging modalities is the rapid practicability and the associated short duration of anesthesia. Tumor-screening can be easily extended to orthotopic mouse models of the abdominal cavity. In therapeutic intervention studies, the ultrasound is used both to normalize the tumor size before the start of the study (comparable tumor volumes) as well as to the longitudinal measurement of tumor volumes as a criterion for therapy responses. Thus, the efficacy of therapies can be tracked in real-time as the study is carried out, as well as the targeted determination of endpoint criteria (for example, new tumor growth after initial response). Abdominal ultrasound examinations with the VeVo3100 can be repeated several times per week. The additional software enables an accurate volume determination which can be performed over a longitudinal period of time.
Next to the morphological and functional imaging, the use of functionalized and targeted Ultrasound- Microbubbles is a fascinating prospect as it combines the potential of localized therapeutic interventions with diagnostic information. This can be achieved even with Bimodal Probes that would be detectable in US and MR and still deliver a therapeutic payload (such as siRNA or AB) into the tumors.