In vivo evaluation of 99mTc-labeled methotrexate-loaded chitosan nanoparticles to visualize tumor foci
Project no. 22199 · Status: Kapanmış · 2020
Summary
Previously, pre-formulation and in vitro cell uptake studies of 99mTc-MT-Chitosan nanoparticles were completed by our Project team in the master's thesis project titled "Development of Tc-99m-labeled Drug Delivery Systems for the Diagnosis of Breast Cancer" and it was determined that its uptake in cancerous cells was more than 6 times that in healthy cells. So, 99mTc-MT-Chitosan nanoparticles were concluded to be promising for use in cancer diagnosis. The aim of this project is to examine the uptake of radiopharmaceutical in tumor tissue by performing in vivo biodistribution studies of 99mTc-MT-Chitosan nanoparticles in healthy and breast cancer modeled experimental animals. For this purpose, MT loaded chitosan nanoparticles were prepared by using different amounts of MT (1, 2.5 and 5mg). The developed MT-Chitosan nanoparticles were evaluated in terms of particle sizes, PdI values, zeta potentials, yields and encapsulation efficiencies. Then, MT-loaded nanoparticles (5mg MT) were labeled with 99mTc radionuclide (1mCi) using stannous tartrate (1mg) as reducing agent and ascorbic acid (0.1mg) as antioxidant agent. As a result of the quality control studies, it was determined that the labeling efficiency was over 99%. In vivo biodistribution studies were performed with 99mTc labeled MT loaded chitosan nanoparticles. Target/non-target tissue uptake rates of 99mTc-MT-Chitosan nanoparticles were compared with 99mTc-MIBI radiopharmaceuticals. As a result of the studies, it was determined that the developed formulations showed uptake more than 5 times in the target tissue at the 4th hour compared to the healthy tissue. The formulation developed as a result of all these studies has; suitable particle size (155.7±3.499 nm), PdI value (0.415±0.068) and zeta potential (+15.7±1.17 mV), suitable preparation efficiency (70.234±2.140), appropriate encapsulation efficiency (50.304 ±2,478), high radiolabeling efficiency (?99%) and high target/non-target tissue uptake (5- fold), its use in the diagnosis of breast cancer was found to be promising. Keywords: Technetium-99m; methotrexate; radiopharmaceutical; breast cancer; Biodistribution.