Laboratory for the Oncotheranostics of the School of Chemical and Biomedical Technologies

The project is aimed at diagnostic radiopharmaceuticals for the patient selection for targeted therapy, as well as the creation of a new class of drugs for targeted therapy of malignant neoplasms, which will make cancer treatment more personalized and, therefore, more effective. The scientific novelty of the project involves in the use of the DARPin (Design Ankyrin Repeat Protein) scaffold protein in the composition of therapeutic radiopharmaceuticals as a target compound, which allows for a higher contrast in molecular imaging of neoplasms and improved therapeutic properties in comparison with antibody-based radiopharmaceuticals.

As part of the research, new methods for the production and quality control of DARPin G3 and Ec1 variants, specific for HER2 and EpCAM tumor markers, respectively, intended for radionuclide imaging, have been developed. The indicated variants of DARPin G3 and Ec1 were developed in the bacterial system. For the DARPin G3 and Ec1 variants, radionuclide treatments for SPECT have been developed and optimized. Preclinical studies of the obtained radioactively labeled variants of DARPin G3 and Ec1 were carried out, including the results of determining the specificity, internalization after binding by tumor cells, affinity, as well as the assessment of biodistribution and preclinical imaging in animal models of ovarian, pancreatic, kidney and breast cancer; data on cumulativeness, general and chronic toxicity were obtained. Methods for the production and quality control of the DARPin-toxin conjugate intended for targeted therapy have been developed; the toxin is accumulated in the bacterial system; the results of its specificity, affinity, internalization into tumor cells were obtained in vitro, and its inhibitory ability was determined. In vivo tests are in progress.

Clinical trials (phase 1) of two drugs were performed to visualize HER2 expression in breast cancer.

Implemented results of research:

Successful clinical trials (phase 1) of two drugs for imaging HER2 expression in breast cancer have been carried out.

Within the framework of the project, two courses were delivered. The first course was organized as a series of open online lectures by Uppsala University employees on the topic "Development of protein-based radiopharmaceuticals for biomedical applications" for students in the areas 18.04.01 Chemical technology, 18.06.01 Chemical technology, 12.06.01 Photonics, instrumentation, optical and biotechnical systems and technologies, 20.03.01 Technosphere safety, 20.04.01 Technosphere safety and RSCBT employees.

Within the framework of the second lecture-practical course, the listeners got acquainted with world practices in the field of working with radiopharmaceuticals. The practical course consisted of an introductory lecture and 8 practical sessions. Based on the results of practical exercises, students will gain knowledge in the areas of "protein labeling and preclinical characteristics", "laboratory analyzes of HPLC and ITLC", "tests for in vitro specificity (uptake, retention, internalization)", "saturation, IC50, proliferation", " biodistribution, in vivo specificity, experiments with double isotopes, autoradiography ”.