Radiosynthesis, molecular modeling and biodistribution of 99mTc-Protoporphyrin as a preclinical model for tumor diagnosis

Abstract

Porphyrins are among the most important and widely used compounds involved in a variety of chemical and biochemical applications. These molecules exhibit very special properties that encourage researchers to label many derivatives with diagnostic or therapeutic radionuclides for medical applications. This study reports the radiolabeling and biodistribution of [Formula: see text]Tc-protoporphyrin IX ([Formula: see text]Tc-PPIX) as a novel potential solid-tumor imaging agent. The factors affecting the radiolabeling process were varied to achieve maximum radiochemical yield. [Formula: see text]Tc-PPIX was obtained in high yield of 97.34 ± 0.21% and high stability in serum up to 24 h. The radiochemical yield of [Formula: see text]Tc-PPIX was assessed by a combination of a paper chromatographic technique and HPLC. A computational analysis for all the potential structures that may be formed due to the interaction between protoporphyrin IX and technetium was performed via the DFT method of calculations in gas phase to predict the most likely structure. Molecular docking was further employed to shed light on the nature of the interaction between the most stable complexes with the target protein. Finally, the in-vivo biodistribution of [Formula: see text]Tc-PPIX complex was evaluated in solid-tumor-bearing mice and high tumor/tissue ratio of 5.17 ± 0.34 at 60 min post injection was obtained. Our finding clearly suggests [Formula: see text]Tc-PPIX as a potential SPECT agent for tumor imaging.