LANTHANIDE IONS toxicity

A compound that is able to influence the relaxation times of water protons has to be paramagnetic. In the Periodic System paramagnetic ions are to be found amongst the transition metals and the rare earth metals (lanthanides). However, it was well known, that the free ions of heavy metals are toxic. Lanthanide ions form soluble complexes with ligands such as phospholipids, amino acids and proteins that are present in plasma. The liver and the skeleton are the major sites of accumulation of free metal ions. Uptake in the liver is mediated by the hepa-tocytes [2]. 

For the application of lanthanide complexes in medical diagnosis and therapy, a general requirement is that the ion Ln3+ and the ligand should remain associated while the complex is in the body, i. e. their dissociation should be minimal, since the free ligand and Ln3+ are toxic. For the dissociation to be negligible, the complexes must be kinetically inert under physiological conditions. Since the complexation properties of the lanthanide ions and Y3+ are quite similar, it is of interest to compare the results obtained as concerns the kinetic behavior of Gd3+ complexes with those known for the complexes of other lanthanides and Y3+. 

Ancillary ligands can dramatically improve detection strategies based on sensitized Ln luminescence by stabilizing the lanthanide to pH variations. Such enhancements in stability and reproducibility allow the use of lanthanide sensors in situ and also potentially in vivo, where free lanthanide ions might precipitate and/or have toxic effects. 

Inorganic phosphors are potential labels for time-resolved luminescence staining and assays in aqueous environment [23, 52-55]. The lanthanide phosphors have essentially infinite shelf life, no toxicity, no photobleaching, and are unaffected by environmental conditions such as pH, temperature, enzymatic reactions, or solvent effects. Their major drawback is that the luminescence per lanthanide ion is significantly less than from the dye-doped or dye nanoparticles due to the weak absorption of individual ions partly compensated by their higher number. Inorganic nanoparticles, however, can be prepared readily in large quantities with relatively simple methods. The size of the nanoparticles can be controlled from low nanometer scale to several hundred nanometers with a narrow size distribution. 

If ytterbium(lll) complexes are to be used in in vivo cellular imaging instead of in in vitro diagnostics, the potential toxicity [30] of lanthanide ions becomes an issue, and the complexes should display low dissociation constants in order to limit the amount of free intracellular lanthanide ions. For instance, the dissociation constant of the Yb -fluorexon complex was found to be comparable to that of the corresponding EDTA complex [7], being higher than DTPA and DOTA complexes, but still limiting the presence of free Yb. However, the cytotoxicity of this luminescent lanthanide complex and its derivatives is not known. 

Toxicity Any deleterious effect of a lanthanide on the living body, usually considered to be a result of the lanthanide ion interfering with enzyme function. 

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