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

Abstract

The biodistribution of an N2 N2 ' 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 (198) Au-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 γ-ray emitted by the (198) Au nucleus was used to follow the biodistribution of the compound in vivo in six male Sprague Dawley rats on a gamma camera. The log Po/w value of the (nat) Au 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 4.5 h 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 t½ for the heart and lungs was greater than 24 h. Excretion of the test compound is seemingly via the kidneys, but is slow with approximately 30% of the ID excreted within 24 h.

Complexities of the interaction of Ni(II), Pd(II) and Pt(II) pyrrole-imine chelates with human serum albumin

“…41 Despite these advances, limited work has been done to elucidate how these compounds bind to human serum albumin (HSA), which is a key step to understanding the plasma distribution of metal chelate drug candidates. 42 HSA is the most abundant plasma protein present at concentrations of around 600 µM. 43 Two of the main functions of HSA are regulating colloidal osmotic pressure and the transportation of exogenous and endogenous compounds.…”

124I Radiolabeling of a AuIII‐NHC Complex for In Vivo Biodistribution Studies

“…[22] Twos tudies used nuclear imaging and 198 Au radiolabelling to examine the biodistribution of Au III complexes bearing (bis)thiosemicarbazone-based and bis(pyrrolide-imine) Schiff base ligands. [23,24] Nevertheless,s uch ar adiolabelling strategy is not ideal to investigate the Au III -to-Au I reduction processes of drug (or prodrug) candidates in animal models,s ince the radioactive signal of 198 Au does not report on the changes within the metal coordination sphere and does not provide information on ligand exchange or loss.…”

124I Radiolabeling of a AuIII‐NHC Complex for In Vivo Biodistribution Studies

“…The study of the biodistribution of Au III compounds in vivo and the evaluation of their metabolization to Au I species is a very challenging task that has not been thoroughly addressed so far, albeit it being a key step in the development of new Au drugs . Two studies used nuclear imaging and 198 Au radiolabelling to examine the biodistribution of Au III complexes bearing (bis)thiosemicarbazone‐based and bis(pyrrolide‐imine) Schiff base ligands . Nevertheless, such a radiolabelling strategy is not ideal to investigate the Au III ‐to‐Au I reduction processes of drug (or prodrug) candidates in animal models, since the radioactive signal of 198 Au does not report on the changes within the metal coordination sphere and does not provide information on ligand exchange or loss.…”