Table of Contents

Israeli Principal Investigator

Prof. Dr. Michal Neeman
Department of Biological Regulation
Weizmann Institute
Rehovot, Israel

DKFZ Principal Investigator

Dr. Tobias Bäuerle
Department of Medical Physics in Radiology
German Cancer Research Center
Heidelberg, Germany

Approaches and Achievements

High resolution imaging of tumor vasculature in an implanted skin chamber using MRI (A) and histological correlation of the tumor (B). Contrast-enhanced MR image in sagittal orientation of the tumor vasculature (arrows; A). In the histological section (blue: tumor cell nuclei, red: tumor vessels; B) the highly vascularized areas of the tumor correspond to the respective MR image. | © dkfz.de

The dependence of tumors on angiogenesis highlights tumor neovasculature as important target for the development of novel approaches for cancer therapy. Non-invasive imaging methods are capable to indicate early therapy effects on vessel morphology, tumor perfusion and permeability as well as on changes in the molecular marker expression. The aims of our project are to study
tumor angiogenesis non-invasively and in vivo (i) in high resolution and (ii) specifically by using molecular probes for MRI.

In order to perform high resolution MR imaging of tumor angiogenesis, a skin chamber model with an integrated RF coil was designed. In this chamber tumor progression including proliferation of tumor cells, development of the neovasculature and infiltration of the mouse stroma can be followed up non-invasively and in vivo. For imaging of blood vessels, a 3D resolution of up to 100 ìm could be achieved by MRI (1.5 Tesla).

For the second aim of our project - to image tumor vessels specifically using MRI - RGD-targeted ultrasmall iron oxide particles (RGD-USPIOs) could be synthesized and applied for assessment of tumor vasculature in vivo by T2* weighted MRI. However, a different cellular uptake by endothelial,
ovarian carcinoma and glioma cells was observed after incubation of these cells with RGDUSPIOs in vitro. In addition, RGD-USPIOs induced a loss of cadherin-dependant intercellular contacts of glioma cells.

In conclusion, tumor vasculature can be imaged non-invasively and in high resolution using a skin chamber model with an integrated MR coil as well as with specifically targeted RGD-USPIOs. However, molecular MR-probes for imaging angiogenesis might induce biological effects including the risk for tumor spread and metastasis.