Vladimir Tolmachev – Scaffold protein-based radionuclide tumour targeting

The main goal of our research is to develop the methodology for using radionuclides in diagnostics and therapy of malignant tumours. Radionuclides can provide information about the molecular composition of the tumour cells and by delivering cytotoxic radionuclides into tumours malignant cells can be eliminated or their growth can be reduced.

Cancer therapy can be improved by identifying specific proteins that are present in the tumour cells but not in normal cells, or that are aberrantly expressed in tumour cells. Already today there are therapies based on the molecular recognition of such proteins by antibodies or inhibitors. However, this kind of targeted therapy is complicated by the varying levels of the aberrantly expressed proteins between patients, or even in a single patient. This warrants the use of methods to identify and image specific proteins in patients.

Radionuclides for molecular targeting of RTK

In our research we develop the use of radionuclides to target and image relevant proteins. Radionuclide imaging is non-invasive and provides important information about proteins in tumours. Specific delivery of cytotoxic radionuclides also has a potential to eradicate malignant cells or, at least, appreciably slow down tumour growth.  

We focus on a group of proteins called receptor tyrosine kinases (RTK) as molecular targets for radionuclide targeting. Abnormal expression of RTK:s is part of the malignant feature and a driving force of cancer growth. Tumour treatments based on the molecular recognition of aberrantly expressed RTK:s by antibodies or RTK inhibitors are already in use but with radionuclide targeting of RTK such treatments can be made more personalised.

Developing methods for radionuclide labelling

Our main strategy is to use engineered scaffold protein-based tracers labelled with radionuclides. Our group pioneered the use of engineered scaffold proteins (affibody molecules) as probes for radionuclide molecular imaging. For particular projects may consider other strategies for delivery of radionuclides to tumour lesions, e.g. the use of monoclonal antibodies, tumour-seeking small molecules, pre-targeting or combined systems.

Our projects also include evaluation of biological aspects of targeting (molecular and cellular biology of a target, radiopharmacology of labelled conjugates) and selection of an optimal radionuclide for a given application. We also work with selection and development of an optimal labelling chemistry, and preclinical evaluation of the produced radiolabeled conjugates.
 

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