Ultra-Sensitive, Switchable MRI Reporters for Lung Metastases
Worldwide Cancer Research
German Cancer Research Center
Early cancer detection and visualisation of disease progression are highly relevant for succesful therapy. Imaging reporters for minimally invasive methods such as MRI are thus an indispensable component and visualising information of the biological complexity of tumour tissue beecomes increasingly important for choosing the right therapy. This is particularly relevant for metastatses detection which is a central aspect of diagnostic imaging. MRI provides excellent soft tissue contrast but suffers from low sensitivity, particularly in the lung which is low in tissue water density but is the most common organ targeted by metastases. MRI reporters with molecular spcificity for metastaes are therefore highly needed but cannot be implemented with conventional detection.  Here we address this problem with an imaging method that includes a pre-targeting approach for LHRH receptor-carrying metastases and subsequent detection through-spin hyperpolarised xenon. The enhanced magnetization of this noble gas together with a saturation transfer technique from the molecular reporter onto the gas will enable ca. 10 million-fold enhanced sensitivity. We will design "smart" nanoparticles that selectively highlight the signal of xenon that has been in contact with these reporters that carry luteinizing hormone-releasing hormone (LHRH) for specific binding to cancer cells. This approach shall visualize pulmonary micrometastates from breast cancer cells. The method serves as an example for a molecular target from which a platform can be developped for different tumour markers. The combination of novel techniques from MRI physics and bioengineering will provide "switchable" MRI agents with a specific MR response frequency for xenon through the metastases-bound reporters and will bring diagnostic lung imaging to an uprecedented sensitivity level. A versatile design respects the need for easy adaptation to implement personalized diagnostics to interrogate the presence of various molecular targets.
4.1 Discovery and preclinical testing of markers and technologies