Uptake of 169Yb complexes in normal and tumour cells: Influence of ligand and metabolic cell activity and stability of cellular association

Kampf, G.; Knop, Gabriel; Franke, W.‐G.; Bergmann, Ralf; Johannsen, B.

doi:10.1016/s0969-8051(97)00010-3

Cited by 3 publications

(8 citation statements)

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“…The occurrence of this eventuality may lead to gross mistakes in the assessment of a study protocol. Interestingly some years ago it was reported that, upon comparing NTA, EDTA and DTPA complexes, the uptake of radioactive Yb-169 into tumor cells decreases in the order of growing complex stability (24). Furthermore, effects associated to the dissociation of Gd-DTPA-BMA were also reported from in vivo investigations either in animal models or in humans (25).…”

mentioning

confidence: 99%

Cellular labeling with Gd(III) chelates: only high thermodynamic stabilities prevent the cells acting as ‘sponges’ of Gd3+ ions

Cabella

Crich

Corpillo

et al. 2006

Contrast Media Mol Imaging

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MR-labeling of cells may be carried out by adding a Gd-based contrast agent to the incubation media. The amount of gadolinium internalized in HTC and C6 cells upon incubation with Gd-DTPA-BMA is circa one order of magnitude higher than those found with Gd-DTPA, Gd-DOTA and Gd-HPDO3A, respectively. The comparison of relaxometric and mass spectrometry determinations allows us to establish that only a minor fraction of intact Gd-DTPA-BMA is internalized into the cells. Moreover the binding/uptake behavior shown by Gd-DTPA-BMA resembles that found when GdCl 3 is added to the incubation medium. We suggest that the lower stability of Gd-DTPA-BMA is responsible for a shift in the dissociation equilibrium that results in the net transfer of Gd 3þ ions on the cell membrane followed by a slower internalization process. The transmetallation process is mediated by components of the incubation media, among which a dominant role is represented by phosphate anions. The uptake of Gd 3þ ions is clearly reflected in the drastic decrease of cell viability observed for cells labeled with Gd-DTPA-BMA.

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mentioning

confidence: 99%

Cellular labeling with Gd(III) chelates: only high thermodynamic stabilities prevent the cells acting as ‘sponges’ of Gd3+ ions

Cabella

Crich

Corpillo

et al. 2006

Contrast Media Mol Imaging

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“…It is only dependent on the metabolic activity of the cells, however, and is not tumor specific [5]. The citrate concentration in blood plasma (% 100 lM) is comparable to Tf (35 lM).…”

Section: Discussionmentioning

confidence: 95%

“…There is an increasing interest in the use of lanthanide in medicine and biology [4][5][6][7]. 169 Yb has been considered as a potential replacement for 125 I and 103 Pd.…”

Section: Discussionmentioning

confidence: 99%

Complexation of ytterbium to human transferrin and its uptake by K562 cells

Zhang

Liu

et al. 2002

European Journal of Biochemistry

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There is an increasing interest in the use of lanthanides in medicine. However, the mechanism of their accumulation in cells is not well understood. Lanthanide cations are similar to ferric ions with regard to transferrin binding, suggesting transferrin-receptor mediated transport is possible; however, this has not yet been confirmed. In order to clarify this mechanism, we investigated the binding of Yb 3+ to apotransferrin by UV-Vis spectroscopy and stopped-flow spectrophotometry, and found that Yb 3+ binds to apotransferrin at the specific iron sites in the presence of bicarbonate. The apparent binding constants of these sites showed that the affinity of Yb 3+ is lower than that of Fe 3+ and binding of Yb 3+ in the N-lobe is kinetically favored while the C-lobe is thermodynamically favored. The first Yb 3+ bound to the C-lobe quantitatively with a Yb/ apotransferrin molar ratio of < 1, whereas the binding to the other site is weaker and approaches completeness by a higher molar ratio only. As demonstrated by 1 H NMR spectra, Yb 3+ binding disturbed the conformation of apotransferrin in a manner similar to Fe 3+ . Flow cytometric studies on the uptake of fluorescein isothiocyanate labeled Yb 3+ -bound transferrin species by K562 cells showed that they bind to the cell receptors. Laser scanning confocal microscopic studies with fluorescein isothiocyanate labeled Yb 3+ -bound transferrin and propidium iodide labeled DNA and RNA in cells indicated that the Yb 3+ entered the cells. The Yb 3+ -transferrin complex inhibited the uptake of the fluorescein labeled ferric-saturated transferrin (Fe 2 -transferrin) complex into K562 cells. The results demonstrate that the complex of Yb 3+ -transferrin complex was recognized by the transferrin receptor and that the transferrin-receptor-mediated mechanism is a possible pathway for Yb 3+ accumulation in cells.Keywords: K562 cells; recognition; transferrin; ytterbium.Lanthanides have been suggested for the treatment of a series of diseases and for diagnosis by magnetic resonance imaging [1,2]. Recent studies also show that they could act as scavengers of free radicals [3] and therefore protect cells and tissues from oxidative stress-induced injury. Some lanthanides nuclides were also suggested for palliative therapy. 169 Yb (c-emission, t ½ % 32 days) was reported to provide comparable tumor control and has been considered as a potential replacement for 125 I and 103 Pd in permanent implants [4,5]. Evidently, the intracellular accumulation is very important in these cases, but its mechanism still remains unclear.It was suggested that the particulate-and protein-bound Ln enters the cells by endocytosis [6]; the anionic lowmolecular-mass complexes, via anion channels [7], whereas free Ln 3+ is transported by ionophores [8], Na + /Ca 2+ exchange [9] and self-facilitated diffusion [10]. It is known that Ln 3+ is mainly bound to proteins in the extracellular media (e.g. plasma). Various studies have demonstrated that considerable amounts of Ln are bound to the iron transport prote...

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“…In any case, inhibitory effects have been reported. Ln 3+ ions at 1 mmol/L inhibit the proliferation of B16 melanoma cells, by arresting the cell transition from the G0/G1 to the S state [33]. According to Ji et al LnCl 3 inhibits proliferation of K562 cells and PAMC82 cells [34], while Chen et al reported that LaCit inhibits proliferation of K562, but not for stomach cancer BGC-823 cells [30].…”

Section: Prevention Of Cancer Developmentmentioning

confidence: 99%

“…The difference was thought to originate in uptake, accumulation, and metabolism. By comparing the uptake of 169 Yb 3+ from citrate and aminopolycarboxylate complexes by V79/4 cells and KTCTL-2 tumor cells, Kampf et al showed that the uptake of Yb citrate is not tumor-specific, whereas, uptake of Yb aminopolycarboxylate complexes is higher by tumor cells and they suggested a different uptake mechanisms for these two compounds [33]. A similar conclusion was drawn from the effects of four Yb 3+ complexes on HeLa cells, HEP-2 cells and malignant tumor cells of human breast compared with diploid cells (human lung embryonic fibroblasts).…”

Section: Selective Cytotoxicitymentioning

confidence: 99%

Lanthanides as Anticancer Agents

Kostova

2005

CMCACA

104

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The application of inorganic chemistry to medicine is a rapidly developing field, and novel therapeutic and diagnostic metals and metal complexes are now having an impact on medical practice. Advances in biocoordination chemistry are crucial for improving the design of compounds to reduce toxic side effects and understand their mechanisms of action. A lot of metal-based drugs are widely used in the treatment of cancer. The clinical success of cisplatin and other platinum complexes is limited by significant side effects acquired or intrinsic resistance. Therefore, much attention has focused on designing new coordination compounds with improved pharmacological properties and a broader range of antitumor activity. Strategies for developing new anticancer agents include the incorporation of carrier groups that can target tumor cells with high specificity. Also of interest is to develop complexes that bind to DNA in a fundamentally different manner than cisplatin, in an attempt to overcome the resistance pathways that have evolved to eliminate the drug. This review focuses on recent advances in developing lanthanide anticancer agents with an emphasis on lanthanide coordination complexes. These complexes may provide a broader spectrum of antitumor activity. They were compared with classical platinum anticancer drugs. Lanthanides are also of interest because of their therapeutic radioisotopes. The dominant pharmacological applications of lanthanides are as agents in radioimmunotherapy and photodynamic therapy.

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Uptake of 169Yb complexes in normal and tumour cells: Influence of ligand and metabolic cell activity and stability of cellular association

Cited by 3 publications

References 14 publications

Cellular labeling with Gd(III) chelates: only high thermodynamic stabilities prevent the cells acting as ‘sponges’ of Gd3+ ions

Cellular labeling with Gd(III) chelates: only high thermodynamic stabilities prevent the cells acting as ‘sponges’ of Gd3+ ions

Complexation of ytterbium to human transferrin and its uptake by K562 cells

Lanthanides as Anticancer Agents

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