title: Structural and in vivo studies of metal chelates of Ga(III) relevant to biomedical imaging.
abstract: The solution chemistry and structure of the complex of the triazamacrocyclic ligand NOTP (1,4,7-triazacyclononane-1,4,7-tris(methylenephosphonate)) with Ga3+ in D2O have been investigated by 1H, 71Ga and 31P NMR spectroscopy. These NMR results show the presence of a 1:1 Ga(NOTP)3- complex, with a highly symmetrical, pseudo-octahedral geometry, possibly with a C3 axis. The 1H spectrum shows that the triazamacrocyclic chelate ring is very rigid, with all the ring protons non-equivalent. The complex is stable in aqueous solution in a wide pH range. Its high thermodynamic stability agrees well with previous results from biodistribution and gamma imaging studies in Wistar rats with 67Ga3+ chelates of triaza macrocyclic ligands, which showed that the neutral chelates 67Ga(NOTA) (where NOTA is 1,4,7-triazacyclononane-1,4,7-triacetate) and 67Ga(NOTPME) (where NOTPME is 1,4,7-triazacyclononane-1,4,7-tris(methylenephosphonate monoethylester)) have similar in vivo behaviour, with high stability and rapid renal excretion, but the high negatively charged 67Ga(NOTP)3- has a considerably slower kidney uptake and elimination.
authors.affiliation: Serviçio de Biofísica e Biomátematica, Fac. Medicina, Univ. de Coimbra, Portugal.
authors.forename: M I
authors.initials: MI
authors.lastname: Prata
authors.forename: A C
authors.initials: AC
authors.lastname: Santos
authors.forename: C F
authors.initials: CF
authors.lastname: Geraldes
authors.forename: J J
authors.initials: JJ
authors.lastname: de Lima
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000737:chemistry*; D005708:Gallium / Q000737:chemistry*; D005710:Gallium Radioisotopes / Q000493:pharmacokinetics*; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000493:pharmacokinetics*; D006573:Heterocyclic Compounds, 1-Ring; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D002614:Chelating Agents; D005710:Gallium Radioisotopes; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; C402168:gallium 1,4,7-triazacyclononane-N,N',N''-tris(methylenephosphonic acid); C068116:1,4,7-triazacyclononane-N,N',N''-tris(methylenephosphonate monoethyl ester); C048993:1,4,7-triazacyclononane-N,N',N''-triacetic acid; D005708:Gallium