Glucose-holmium for radiotherapy: Characterization and in vitro assays

Abstract

Background The existence of saccharide-holmium complexes, containing mono or polysaccharide molecules, is an attractive hypothesis toward a radiation therapy (RT) with beta-emitters targeting high glucose metabolic human sites. To exam such hypothesis, the aim of this study was to investigate the possible chemical interactions of Ho and glucose molecules and if glucose may be a facilitator to holmium cell internalization based on in vitro uptake assays and mass spectrometry analyses.

Methods The ionic-solution preparations were based on glucose-anhydrous and holmium-nitrate hydrated in aqueous solution, in non-radioactive condition. The uptakes in MDAMB231 cell lineage were evaluated, at 0 and 50 µg mL−1 holmium solution, in incubation times of 10, 30 and 50 min. The measurements of the holmium mass into the dried cell were evaluated by Neutron Activation Analysis – NAA method. Also, the ionic solution was tested in Electrospray Ionization Mass Spectrometry (ESI-MS) in order to identify Ho and glucose interactions.

Results There were intracellular holmium-uptake in MDAMB-231 of 3.6 ± 0.1, 6.8 ± 0.2 and 9.7 ± 0.3 μg increasing linearly with incubation time. The m/z ions at 523, 586, 649, 991 and 1054 were attributed to the positively loaded species containing Ho+3, glucose (GLU) and NO3-, making up the possible molecular compound formulae, involving Ho, GLU, and anions.