title: 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.
authors.affiliation: School of Chemistry and Physics, University of KwaZulu-Natal, Private Bag X01, Pietermaritzburg, 3209, South Africa.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Akerman
authors.forename: Orde Q
authors.initials: OQ
authors.lastname: Munro
authors.forename: Modisenyane
authors.initials: M
authors.lastname: Mongane
authors.forename: Johan A
authors.initials: JA
authors.lastname: van Staden
authors.forename: William I D
authors.initials: WI
authors.lastname: Rae
authors.forename: Cornelius J
authors.initials: CJ
authors.lastname: Bester
authors.forename: Biljana
authors.initials: B
authors.lastname: Marjanovic-Painter
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Szucs
authors.forename: Jan Rijn
authors.initials: JR
authors.lastname: Zeevaart
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D006046:Gold / Q000737:chemistry*; D006207:Half-Life; D006801:Humans; D007097:Imines / Q000737:chemistry*; D007553:Isotope Labeling; D008297:Male; D009942:Organometallic Compounds / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D011854:Radiochemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012545:Schiff Bases / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D007097:Imines; D009942:Organometallic Compounds; D012545:Schiff Bases; D006046:Gold
keywords: 198Au; Schiff base; biodistribution; gold(III); radiolabelling