ABSTRACT
The development of novel gold-198 complexes with water-soluble phosphines is reported. A series of cationic and hydrophilic 198Au complexes containing the ligands tris(hydroxymethyl)phosphine (THP, 1) 1,2-bis[bis(hydroxymethyl)phosphino]benzene (HMPB, 2), and 1,2-bis[bis(hydroxymethyl)phosphino]ethane (HMPE, 3) were prepared and evaluated as models for potential gold-199 radiopharmaceuticals. The 198Au complexes were formed in high radiochemical purity by simply mixing H198AuCl4 with the respective ligand. The complexes were shown to exhibit high in vitro stability over wide pH ranges and temperatures. However, only the 198Au(HMPB)2+ complex was found to exhibit good in vivo stability. HPLC analyses indicated that the 198Au complexes with these three phosphine ligands produced singular species with similar retention times as compared to their known macroscopic complexes.
Subject(s)
Gold Radioisotopes/chemistry , Phosphines/chemical synthesis , Radiopharmaceuticals/chemistry , Animals , Drug Stability , Gold Radioisotopes/therapeutic use , Humans , Hydrogen-Ion Concentration , Isotope Labeling , Phosphines/pharmacokinetics , Phosphines/therapeutic use , Radiopharmaceuticals/therapeutic use , Rats , Rats, Sprague-Dawley , Tissue DistributionABSTRACT
The water-soluble, monophosphine ligand tris(hydroxymethyl)phosphine (THMP) was complexed with 99mTc. The 99mTc-THMP was formed in high radiochemical purity by simply mixing 99mTcO4- with THMP over a wide pH range. In vitro and in vivo studies indicated the complex to be highly stable under the respective conditions. HPLC analysis indicated a singular species with a retention time identical to the known [ReO2(THMP)4]1 complex. Results show that the hydroxymethylphosphine functionality is attractive for use in designing new 99mTc radiopharmaceuticals.
