Design, Synthesis, Biological Evaluation, DFT Calculations, and Molecular Docking Investigations of ^99mTc-Rosuvastatin as a Promising Radiopharmaceutical for Liver Targeting

Rosuvastatin is a lipid-lowering medication belonging to the statin group that acts as a selective inhibitor of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase, a rate-limiting step of cholesterol biosynthesis in the liver. ^99mTc-rosuvastatin was synthesized aiming to develop a potential radiopharmaceutical for targeting liver. The in vitro stability and radiochemical yield were investigated, and the yield of the ^99mTc-rosuvastatin complex was 89.5 ± 1.85%. Biodistribution study revealed a good preferential localization of ^99mTc-rosuvastatin in liver tissues suggesting using the labeled compound as a promising liver imaging candidate. The favorable sites of Tc labeling were determined by the analysis of natural atomic charges using the DFT method at the B3LYP/LanL2DZ level of theory. Binding modes between the rosuvastatin (and its stable technetium complex) and the human HMG-CoA reductase were determined using molecular docking, and the obtained results revealed the effectiveness of technetium in increasing the binding affinity to the active residues of HMG-CoA reductase.