title: A triazacyclononane-based bifunctional phosphinate ligand for the preparation of multimeric 68Ga tracers for positron emission tomography.
abstract: For application in positron emission tomography (PET), PrP9, a N,N',N''-trisubstituted triazacyclononane with methyl(2-carboxyethyl)phosphinic acid pendant arms, was developed as (68)Ga(3+) complexing agent. The synthesis is short and inexpensive. Ga(III) and Fe(III) complexes of PrP9 were characterized by single-crystal X-ray diffraction. Stepwise protonation constants and thermodynamic stabilities of metal complexes were determined by potentiometry. The Ga(III) complex possesses a high thermodynamic stability (log K([GaL])=26.24) and a high degree of kinetic inertness. (68)Ga labeling of PrP9 is possible at ambient temperature and in a wide pH range, also at pH values as low as 1. This means that for the first time, the neat eluate of a TiO(2)-based (68)Ge/(68)Ga generator (typically consisting of 0.1 M HCl) can be directly used for labeling purposes. The rate of (68)Ga activity incorporation at pH 3.3 and 20 degrees C is higher than for the established chelators DOTA and NOTA. Tris-amides of PrP9 with amino acid esters were synthesized to act as models for multimeric peptide conjugates. These conjugates exhibit radiolabeling properties similar to those of unsubstituted PrP9.
authors.affiliation: Department of Nuclear Medicine, Technische Universität München, Ismaninger Str. 22, 81675 München, Germany. johannes.notni@tum.de
authors.forename: Johannes
authors.initials: J
authors.lastname: Notni
authors.forename: Petr
authors.initials: P
authors.lastname: Hermann
authors.forename: Jana
authors.initials: J
authors.lastname: Havlícková
authors.forename: Jan
authors.initials: J
authors.lastname: Kotek
authors.forename: Vojtech
authors.initials: V
authors.lastname: Kubícek
authors.forename: Jan
authors.initials: J
authors.lastname: Plutnar
authors.forename: Natalia
authors.initials: N
authors.lastname: Loktionova
authors.forename: Patrick Johannes
authors.initials: PJ
authors.lastname: Riss
authors.forename: Frank
authors.initials: F
authors.lastname: Rösch
authors.forename: Ivan
authors.initials: I
authors.lastname: Lukes
mesh_terms: D005709:Gallium Isotopes / Q000737:chemistry*; D007501:Iron / Q000737:chemistry*; D007553:Isotope Labeling; D008024:Ligands; D047028:Macrocyclic Compounds / Q000737:chemistry*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D010721:Phosphinic Acids / Q000737:chemistry*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D005709:Gallium Isotopes; D008024:Ligands; D047028:Macrocyclic Compounds; D009942:Organometallic Compounds; D010721:Phosphinic Acids; D019275:Radiopharmaceuticals; D007501:Iron