Development of engineered target-specific microproteins as molecular imaging agents

Development of engineered target-specific microproteins as molecular imaging agents

Molecular imaging using radiopharmaceuticals enables non-invasive visual representation of disease processes in vivo  at the molecular level. It allows the visualization of the decay of radioactive isotopes with various highly sensitive methods (e.g. scintigraphy, positron-emission-tomography (PET) or single photon emission computed tomography (SPECT)).

In cancer diagnosis, radiotracers can be used, for example, which track the increased metabolism of the tumor. Moreover, radiopharmaceuticals are being developed in which the radionuclides are linked to so-called ‘targeting’ components via chelators. Then these selectively bind to highly expressed target structures on the tumor cells, thus enabling a site-directed therapeutic effect.

Cystine-knot microproteins (Microbodies™/Knottins) are an innovative class of these kinds of targeting components. The artificial binding proteins, which are approximately 3-5 kDa large and can be manufactured both recombinantly and chemically, thus are well-suited for the targeted conjugation with radionuclides. Due to their small size and stable cystine-knot structure, they also have favorable properties for the clinical development of radiopharmaceuticals.

The aim of this project is to develop microprotein-based radionuclide-conjugates to address cancer-specific targets. Within the framework of the project, new microproteins are to be identified with the help of evolutive and rational protein design and conjugated to different radionuclides. In the medium term and in addition to initial lead compounds, this project plans to build a functional platform according to industry standards which will allow for the development of lead compounds that are suitable for drugs. Over the long term, this will enable the development of radiopharmaceuticals for non-invasive diagnosis (in vivo imaging) and/or the treatment of tumor diseases.