Gd-GLU toward NMR imaging: synthesis, characterization and breast cell uptake assay

Abstract

Breast cancer cell uptake of Gd-metal is investigated based on the formation of coordinate compounds of gadolinium and glucose (Glu) molecules in solution. The hypothesis is that glucose helps Gd-internalization by complex formations constituted of Gd3+ coordinate to m-glucose molecules, whose valence was complemented by Cl- anions. Such a proposal is an insight toward a metabolic-dependent contrast-agent for cancer and inflammation in magnetic resonance image. A solution was prepared based on anhydrous d-glucose and gadolinium chloride (Gd-Glu). Uptake assays for MDA-MB-231(c231) cells were elaborated collecting incubated c231-cells with Gd-Glu and measuring metal-uptake and their concentrations by Nuclear Activation Analysis (NAA). The ionic solution was studied using Direct-Infusion Electrospray Ionization Mass-Spectrometry (ESI-MS) to identify Gd-Glu interactions. Means and standard deviations of Gd-masses were 13.3±0.8 and 12.5±0.7µg, at 361.5 µg of Gd in 3mL Gd-Glu/PBS solution, in times of 30-50 min, equivalent to the concentrations of 13404±2104 and 11347±2742 µg.g-1 in dried cells. Such values were statistically higher than the control with metal presence. ESI-MS demonstrated the m/z-signals at 516, 552, 696, 923, attributed to positively loaded-species containing Glu, Gd+3 and Cl-. In conclusion, Gd-internalization was increased in aqueous solution due to the gadolinium-glucose coordination. Such findings drive the research to MRI with Gd-Glu complexes.

Keywords

• Glucose
• Gadolinium
• Breast cancer
• In vitro uptake
• MDA-MB-231