Synthesis, characterization and density functional theory of 64Cu based complex for hypoxia imaging

An important contributing factor to the growth of aggressive and treatment-resistant tumors is tumor hypoxia. In this investigation, we created a unique tracer, ⁶⁴Cu-biacetyl-bis(4-methyl-3-semicarbazone) Complex (⁶⁴Cu-[APSC]₂), for hypoxia imaging. Numerous spectral and electrochemical analyses were used to characterize the synthesized ligand and its metal complex. The coordination of the metal in the metal complex was also supported by DFT (B3LYP model) calculations. The radiochemical yields and purities of ⁶⁴Cu-[APSC]₂ were found to be quantitative, as determined by TLC and HPLC analyses.

Stability studies in human plasma demonstrated that ⁶⁴Cu-[APSC]₂ remained steady for at least four hours while being incubated at 37 °C. MDA-MB-231 cell-line xenografts were placed in nude mice for biodistribution research. The results revealed significant accumulation of the tracer in tumors after 2 h post-injection, which correlated with the redox potential and reactive oxygen species. These findings suggest that ⁶⁴Cu-[APSC]₂ shows promising evidence as a theranostic radiopharmaceutical for hypoxic tumors.