Skräddarsydda proteiner för tumörmålsökning med radionuklider
Tidsperiod: 2016-01-01 till 2019-12-31
Projektledare: Vladimir Tolmachev
Medarbetare: Anna Orlova, Stefan Ståhl, Sophia Hober, Amelie Eriksson Karlström
Budget: 6 000 000 SEK
A promising approach to treatment of disseminated cancer is a targeting, i.e. therapy based on specific recognition of cancer-associated molecular alteration in tumour cells. Success of the targeting therapy depends on a correct identification of patients with tumours expressing particular molecular targets. Current methods for molecular profiling of tumours cannot provide the required information in a reliable way.Radionuclide imaging of therapeutic targets may enable patient stratification for and response monitoring of targeting therapies making cancer treatment more personalized. Availability of sensitive and specific imaging probes is crucial for clinical implementation of radionuclide molecular imaging. The goal of the project is to provide sensitive molecular probes for radionuclide imaging.We plan to use engineered scaffold proteins (ESP) as imaging probes. Affibodies and ADAPTs are a novel type of scaffold proteins, which has been developed by researchers at Royal Institute of Technology (KTH), Stockholm. High affinity, small size and high structural stability of affibodies and ADAPTs make them suitable as targeting agents for radionuclide diagnostics of malignant tumours. The applicant’s group pioneered in evaluation of affibodies and ADAPTs for radionuclide imaging purposes. A high potential of affibody molecules for radionuclide molecular imaging was demonstrated in a number of pre-clinical studies and confirmed in proof-of-principle clinical studies.We plan to investigate systematically factors influencing biodistribution of affibody molecules. Labelling chemistry, i.e. chemical and physicochemical properties of nuclides and chelators for their coupling to affibodies, and modification non-binding amino acids will be clarified. For ADAPTs, only preliminary data are available. This necessitates intensive evaluation of factors influencing biodistribution and targeting properties of ADAPTs, including effect of dimerization, position of a label, and nature of radiocatabolites. Sudies will be performed at Uppsala University and supported by researchers from Royal Institute of Technology. The research is planned for five years. The data obtained within the project would enable to develop tumour-targeting ESP with an improved sensitivity and pre-determined biological properties. The information obtained within this project can be used for development of radionuclide labelling of other types of small scaffold affinity proteins for tumour targeting, facilitating the application of these proteins in medicine and biology.