Synthesis of a radiopharmaceutical for diagnosis and therapy of rheumatoid arthritis

Abstract

Background. A conjugate consisting of methotrexate and a bifunctional chelating agent was synthesized. This compound is distinguished by its ability to target foci of autoimmune arthritis.

Aim. To synthesize a radionuclide ¹⁷⁷Lu-based complex for the treatment of autoimmune arthritis.

Methods. After synthesis, the radiochemical purity of the complex was determined by thin layer chromatography. In the in vivo study, 12 outbred male rats were used as a test system. Prior to the biodistribution study, the animals were divided into a control group and a study group. The radioconjugate biodistribution was assessed with the generally accepted method of direct radiometry by direct comparison of radiopharmaceutical distribution in blood and organs. Taking into account the ¹⁷⁷Lu half-life, at least three animals were assessed at measurement points when studying the radiopharmaceutical pharmacokinetics and biodistribution.

Results. The radiochemical purity of the ¹⁷⁷Lu-based complex was no less than 95%. Biodistribution studies showed a tendency towards radioactivity accumulation in the kidneys, heart, and lungs. In the remaining assessed organs and tissues, the radioactivity accumulation was moderate and transient. The therapeutic radiopharmaceutical demonstrated a satisfactory effectiveness in relation to the target nosology, autoimmune arthritis, evident as clinically significant improvement and partial restoration of the functions of the affected limb.

Conclusion. The results of the study can be implemented in the practice for the development of drugs and medical devices and justify conducting an expanded study and optimizing the mechanisms for targeted action of the radiopharmaceuticals, such as studied in the present work.