title: Novel [99mTcIII(PS)2(Ln)] mixed-ligand compounds (PS = phosphino-thiolate; L = dithiocarbamate) useful in design and development of TcIII-based agents: synthesis, in vitro, and ex vivo biodistribution studies.
abstract: A general procedure for the preparation of a new class of neutral six-coordinated mixed ligand [(99m)Tc(III)(PS)2(Ln)] compounds (PS = trisalkyl-phosphino-thiolate; Ln = dithiocarbamate) is reported as well as their in vitro stability and the ex vivo tissue distribution studies. [(99m)Tc(PS)2(Ln)] complexes were prepared in high yield in nearly physiologic conditions following a one-pot procedure. For instance, the chemical identity of [(99m)Tc(PSiso)2(L1)] (PSiso = 2-(diisopropylphosphino)ethanethiol; L1 = pyrrolidine dithiocarbamate) was determined by HPLC comparison with the corresponding (99g)Tc-complex. All complexes comprise the stable [(99m)Tc(III)(PS)2](+) moiety, where the remaining two coordination positions are saturated by a dithiocarbamate chelate, also carrying bioactive molecules (e.g., 2-methoxyphenylpiperazine). [(99m)Tc(PS)2(Ln)] complexes were inert toward ligand exchange reactions. No significant in vitro and in vivo biotransformation were observed, underlining their remarkable thermodynamic stability and kinetic inertness. These results could be conveniently utilized to devise a novel class of (99m)Tc(III)-based compounds useful in radiopharmaceutical applications.
authors.affiliation: Dipartimento di Scienze Chirurgiche, Oncologiche e Gastroenterologiche, Università degli Studi di Padova , via Gattamelata 64, 35138 Padua, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Salvarese
authors.forename: Nicolò
authors.initials: N
authors.lastname: Morellato
authors.forename: Antonio
authors.initials: A
authors.lastname: Rosato
authors.forename: Laura
authors.initials: L
authors.lastname: Meléndez-Alafort
authors.forename: Fiorenzo
authors.initials: F
authors.lastname: Refosco
authors.forename: Cristina
authors.initials: C
authors.lastname: Bolzati
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008024:Ligands; D008297:Male; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D013667:Technetium / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D008024:Ligands; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D013667:Technetium