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

Ilza Dalmazio,Rodiney Augusti,Tarcisio Passos Ribeiro De Campos,Iassudara Garcia Almeida

doi:10.1590/s2175-97902019000318122

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.

Highlights

The viability of providing a diagnosis with contrastagents, supported by nuclear magnetic resonance images and guided to tissues that present high glucose metabolism, is attractive and justifies the search for molecular-tracers as an agent for screening small high metabolic sites
The high uptake of Glu by their GLUT-transporters play a role in the metabolism of c231 cancerous cells. At this stage of research development, the present paper addresses the synthesis of glucose and gadolinium chloride (Gd-Glu) complexes in aqueous solution, their characterization by Electrospray Ionization Mass Spectrometry, and the in vitro tests
The cells were kept under glucose deprivation, seeking to reproduce a condition similar to that specified in PET-FDG humans protocols of 24 h with no exercise, no carbohydrates, 40% of normal daily water consumption, and 6 h total fasting prior exams

Summary

Introduction

The viability of providing a diagnosis with contrastagents, supported by nuclear magnetic resonance images and guided to tissues that present high glucose metabolism, is attractive and justifies the search for molecular-tracers as an agent for screening small high metabolic sites. Such procedure excludes radionuclides; there would not be radiotoxicity and radioprotection involvements. There would be no restriction of its application as a contrast agent Such protocols may generate medical information that can be able to overlap the diagnosis with PET - Positron Emission Tomography with fluordeoxyglucose, reproducing similar medical analyses. There would be a perspective to have MRI taking care of the diagnosis of some diseases based on the evaluation of metabolic-sugar uptake as in inflammations, small tumors or metastasis, with a lesser cost and increased safety

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