Biodistribution (as determined by the radiolabelled equivalent) of a gold(III) bis(pyrrolide-imine) Schiff base complex: a potential chemotherapeutic

摘要

The biodistribution of an N2N2 tetradentate gold(III) chelate, which is known to be cytotoxic towards a range of human cancer cell lines, was determined by a radiolabelled equivalent of the compound. The Au-198-labelled gold(III) chelate of a bis(pyrrolide-imine) Schiff base ligand with a three-carbon di(azomethine) linkage was successfully synthesised with a high radiochemical yield of 73% and radiochemical purity of >95%. The high energy -ray emitted by the Au-198 nucleus was used to follow the biodistribution of the compound in vivo in six male Sprague Dawley rats on a gamma camera. The log P-o/w value of the Au-nat analogue, -1.92(2), showed that the compound is hydrophilic and therefore likely to largely remain in the blood pool. This was confirmed by the biodistribution study, which showed 21% of the injected dose (ID) remained in the blood pool 4.5h after injection. This decreased to 10.8% over a 24-h period. The activity measured in the lungs, 1.48%ID/g, remained relatively constant over a 24-h period suggesting that the complex had accumulated in the lungs in the form of particulates, and could not be cleared by the test subjects. The t(1/2) for the heart and lungs was greater than 24h. Excretion of the test compound is seemingly via the kidneys, but is slow with approximately 30% of the ID excreted within 24h.