Speaker
Mr
Jan Holub
(Charles University in Prague, Faculty of Science, Department of Inorganic Chemistry, Czech Republic)
Description
This work reports on synthesis, complexation and radiolabeling study of new macrocyclic ligands for selective complexation of gallium, which might serve as potential radiopharmaceuticals for 68Ga-PET bone imaging. Bone-targeting bis(phosphonic) acid moiety, as a distant, non-coordinating group was appended to the 1,4,7-triazacyclonone-1,4-diacetic acid macrocyclic fragment through acetamide or methylphosphinic spacer. Complexation of Ga(III) was studied under different temperature and pH levels by means of 71Ga, 31P and 1H NMR spectroscopy. Complex formation proceeds through intermediate steps involving bis(phosphonate) coordination. Hydrolysis of amide bond of the carboxoamidebis(phosphonate) was also observed during the complexation reaction, leading to the Ga(III)-NOTA complex, confirmed by X-ray diffraction. Under all tested conditions, ligand with methylphosphinate linker showed faster complexation rate than the acetamide. Results from NMR studies (milimolar concentrations) were comparable with gallium-68 radiolabeling study (picomolar concentrations). In vitro sorption study showed effective binding of the complexes to hydroxyapatite, which was used as a model of real bone tissue. Selective bone uptake was confirmed by in vivo PET imaging on laboratory rats.
Primary author
Mr
Jan Holub
(Charles University in Prague, Faculty of Science, Department of Inorganic Chemistry, Czech Republic)
Co-authors
Prof.
Frank Roesch
(Institute of Nuclear Chemistry, University Mainz, Fritz-Strassmann-Weg 2, 55128 Mainz, Germany)
Marian Meckel
(Institute of Nuclear Chemistry, University Mainz, Fritz-Strassmann-Weg 2, 55128 Mainz, Germany)
Prof.
Petr Hermann
(Charles University in Prague, Faculty of Science, Department of Inorganic Chemistry)
Mr
Vojtěch Kubíček
(Charles University in Prague, Faculty of Science, Department of Inorganic Chemistry)
