The anti-tumour properties and biodistribution (as determined by the radiolabeled equivalent) of Au-compounds intended as potential chemotherapeutics

• Published in: Applied radiation and isotopes Vol. 67; no. 7; pp. 1370 - 1376
• Main Authors: Nell, M.J., Wagener, J.M., Zeevaart, J.R., Kilian, E., Mamo, M.A., Layh, M., Coyanis, M., van Rensburg, C.E.J.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-07-2009
• Subjects: Animals; Anti-tumour activity; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacokinetics; Au-compounds; Biodistribution; Cell Line, Tumor; Cell Proliferation - drug effects; Drug Screening Assays, Antitumor; Humans; Hydrophobic and Hydrophilic Interactions; Organogold Compounds - pharmacokinetics; Phosphines; Radioactive tracers; Tissue Distribution; Anti-tumour activity; Radioactive tracers; Au-compounds; Biodistribution
• ISSN: 0969-8043; 1872-9800
• DOI: 10.1016/j.apradiso.2009.02.035

The anti-tumour activity of the Au (I) phosphine complex [Au(dppe
2]Cl was first discovered in the mid 1980s although promising results were obtained it did not pass clinical studies because of its toxicity to organs such as the liver and heart. The aim of this study was to determine whether the two novel gold compounds (MM5 and MM6), selected for this study, have higher selectivity for cancer cells with less toxicity towards normal cells than [Au(dppe)
2]Cl, and also to determine whether they have improved bio distribution compared to [Au(dppe)
2]Cl. The Au-compounds as potential chemotherapeutic drugs were evaluated by using radioactive tracers in the
in vitro and
in vivo studies.
Results obtained from these experiments showed that the uptake of these experimental compounds was dependent on their octanol/water partition coefficient. However; the inhibition of cell growth did not correlate with the uptake of these compounds by the cells that were tested.
In terms of the total uptake it was found that the compounds that were less lipophilic (MM5, MM6) were taken up less efficiently in cells than those that are more lipophilic. Therefore hydrophilic drugs are expected to have a limited biodistribution compared to lipophilic drugs. This might imply a more selective tumour uptake.