198Au-labeled hydroxymethyl phosphines as models for potential therapeutic pharmaceuticals

The development of novel gold-198 complexes with water-soluble phosphines is reported. A series of cationic and hydrophilic Au-198 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 Au-198 complexes were formed in high radiochemical purity by simply mixing (HAuCl4)-Au-198 with the respective ligand. The complexes were shown to exhibit high in vitro stability over wide pH ranges and temperatures. However, only the Au-198(HMPB)(2)(+) complex was found to exhibit good in vivo stability. HPLC analyses indicated that the Au-198 complexes with these three phosphine ligands produced singular species with similar retention times as compared to their known macroscopic complexes. NUCL MED BIOL 25;6: 577-583 1998. (C) 1998 Elsevier Science Inc.