GC-04. Studies on therapeutic potential of a radiopharmaceutical based on polymer capsules with incorporated 188Re isotope for the treatment of inflammatory joint diseases
Alisa S. Postovalova1,2, Timofey E. Karpov1,2, Nikolay A. Kostenikov2, Dmitry S. Sysoev2, Dmitry O. Antuganov2, Darya R. Akhmetova1,2, Albert R. Muslimov1, Alexander S. Timin1,2
1 Peter The Great St. Petersburg Polytechnic University, St. Petersburg, Russia
2 A. M. Granov Russian Research Center of Radiology and Surgical Technologies, St. Petersburg, Russia
Contact: Dr. Alisa S. Postovalova, phone: +7 (922) 155-83-02, e-mail: alisa_postovalova@mail.ru
Summary
Arthritis is a heterogeneous group of diseases that affect one or more joints and are caused by inflammatory damage of various genesis, by involving the synovial membrane, capsule, cartilage and other components of the joint. Inflammatory diseases of the joints (IDJ) occur in 0.3-3% of the population worldwide. In particular, they affect 21% of adults in Russia. The joint swelling, stiffness of movements and chronic pain are observed in arthritis, thus altering normal working capacity, and often leading to disability. Development of novel drugs for the treatment of arthritis is an urgent task, due to variety of the IJD lesions and common inefficiency of basic, biological and glucocorticosteroid therapy. Radiopharmaceuticals show a number of advantages over radiation and chemotherapy used in the IDJ treatment. Hence, the aim of the study was to develop a radiopharmaceutical of a complex composition and evaluate its therapeutic effect in the animal model of arthritis.
Materials and methods
The 188Re-PLA-MPs preparation was developed in the form of 188Re-labeled polymer carriers. Basic properties of the carriers, their toxicity and safety were assessed, as well as the drug biodistribution. The results of the drug stability testing and its retention at the injection site were registered by SPECT and PET-CT images taken on the 1st, 2nd, 3rd and 7th day of the study, as well as by direct radiometry with measurement of the radioactive signal (%ID/g). Therapeutic efficacy of the radiopharmaceutical was evaluated in a model of inflammatory disease of large joints in the Wistar rats by measuring changes in the joint diameter and histology examination. The data on expression of proinflammatory cytokines were found to be consistent with histological data.
Results
The biodistribution experiments have shown that 98% of the radioactive drug remained at the injection site, without penetrating healthy tissues. Biological effects of the drug in the IDJ treatment was shown by means of the joint sizing, measurements of inflammatory blood cytokines and histological analysis.
Conclusion
According to experimental results, the developed radiopharmaceutical has shown its efficiency in the animal model of inflammatory joint disease produced in Wistar rats, thus providing a basis for further studies in this area.
Keywords
Arthritis, synovectomy, microcarriers, radionuclide therapy, rhenium.
