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

Scientific results:

In the course of preclinical and clinical studies targeted conjugates for radionuclide imaging and therapy of malignant tumors:

1. Preclinical development of a number of labeled compounds based on a scaffold protein technology platform using DARPin, ADAPT6 and affibody scaffolds for visualization of molecular targets of HER2 and EpCAM was performed. All developed radiopharmaceuticals have no analogues in world practice. They provide significantly better contrast of imagining of selected targets than alternative tracers.
2. Clinical trials (phase I) of radiopharmaceuticals ^99mTc-DARPin G3 and ^99mTc-ADAPT6 were conducted. The use of both tracers allows the differentiation of HER2-positive and HER2-negative breast tumors by the method of SPECT. This creates the prerequisites for personalized breast cancer treatment.
3. The targeted toxin DARPin Ec1-LoPE, which has been  developed during the study, binds to cell lines expressing EpCAM with high affinity and is highly toxic for malignant cells. Experimental therapy in mice significantly slows down the growth of tumors expressing EpCAM. The addition of Ec1-LoPE to therapy using the monoclonal antibody trastuzumab for tumors expressing both EpCAM and HER2 increases the effect of such therapy.
4. The targeted toxin DARPin G3-LoPE, which has been developed during the study, binds to cancer cell lines expressing HER2 with high affinity. Experimental therapy in mice significantly slows down the growth of tumours expressing HER2. The combination of therapies using DARPin G3-LoPE and the monoclonal antibody trastuzumab is undesirable.
5. Preclinical studies of the functional suitability of ¹⁸⁸Re-ZHER2:41071 for therapy and the dosimetric aspects of its safety have been conducted. Anti-tumour efficacy of ¹⁸⁸Re-ZHER2:41071 was  demonstrated in preclinical murine models.
6. A comparative clinical evaluation of the use of ^99mTc-DARPin G3 and ^99mTc-ADAPT6 for visualization HER2 expression in breast cancer was performed. At selected time points [^99mTc]Tc-ADAPT6 has significantly higher uptake in soft tissue metastases, which may be an advantage for imaging small metastases.
7. Clinical studies of the drug ^99mTc-maSSS-RM26 have been conducted. SPECT imaging of GRPR expression using [^99mTc]Tc-SSS-RM26 can be used

Implementation of research results:

The results of preclinical and clinical studies formed the basis of the project "Radiopharmaceutical medicines based on Scaffolds for the diagnosis and therapy of tumors with HER2/neu overexpression" within the Unified Sectoral Thematic Plan Rosatom Research and Development Center. The project was supported by the Scientific Council of Rusatom Healthcare  (dated 11/24/2022). Rusatom Healthcare  agreed to act as the customer of the work under the R&D contract. 

Organizational and infrastructural changes:

The Oncoteranostics Research Center has been established, which is the center of competence in the field of personalized medicine at the national level.

Education and personnel occupational retraining:

An educational module "Development of protein-based radiopharmaceuticals for biomedical use" was created for students and postgraduates of Russian organizations in the field of scientific research, which includes a cycle of 10 lectures and 13 practical classes. This module is intended for students in the fields of 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.

Cooperation:

• National Research Centre "Kurchatov Institute"
• Siberian State Medical University
• MIREA - Russian Technological University
• Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences
• Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences