title: A bisphosphonate monoamide analogue of DOTA: a potential agent for bone targeting.
abstract: A new macrocyclic DOTA-like ligand (BPAMD) for bone imaging and therapy containing a monoamide bis(phosphonic acid) bone-seeking group was designed and synthesized. Its lanthanide(III) complexes were prepared and characterized by 1H and 31P NMR spectroscopy. The Gd(III)-BPAMD complex was investigated in detail by 1H and 17O relaxometric studies to inspect parameters relevant for its potential application as an MRI contrast agent. Sorption experiments were conducted with Gd(III) and Tb(III) complexes using hydroxyapatite (HA) as a model of bone surface. Very effective uptake of the Gd-BPAMD complex by the HA surface was observed in NMR experiments. Radiochemical studies with the (160Tb-BPAMD)-HA system proved the sorption to be remarkably fast and strong on one hand and fully reversible on the other hand. The strong (Gd-BPAMD)-HA interaction was also supported by 1H NMRD measurements in the presence of a hydroxyapatite slurry, which showed an increase of the rotational correlation time upon adsorption of the complex on the HA surface, resulting in a significant relaxivity enhancement. The amide-bis(phosphonate) moiety is the only factor responsible for the binding of the complex to HA.
authors.affiliation: Laboratory of Organic Chemistry and Catalysis, Delft University of Technology, Julianalaan 136, 2628 BL Delft, The Netherlands.
authors.forename: Vojtech
authors.initials: V
authors.lastname: Kubícek
authors.forename: Jakub
authors.initials: J
authors.lastname: Rudovský
authors.forename: Jan
authors.initials: J
authors.lastname: Kotek
authors.forename: Petr
authors.initials: P
authors.lastname: Hermann
authors.forename: Luce
authors.initials: L
authors.lastname: Vander Elst
authors.forename: Robert N
authors.initials: RN
authors.lastname: Muller
authors.forename: Zvonimir I
authors.initials: ZI
authors.lastname: Kolar
authors.forename: Hubert Th
authors.initials: HT
authors.lastname: Wolterbeek
authors.forename: Joop A
authors.initials: JA
authors.lastname: Peters
authors.forename: Ivan
authors.initials: I
authors.lastname: Lukes
mesh_terms: D000327:Adsorption; D000577:Amides / Q000737:chemistry* / Q000493:pharmacokinetics; D001667:Binding, Competitive; D001672:Biocompatible Materials / Q000737:chemistry; D001842:Bone and Bones / Q000737:chemistry*; D002614:Chelating Agents / Q000737:chemistry* / Q000493:pharmacokinetics; D004164:Diphosphonates / Q000737:chemistry* / Q000493:pharmacokinetics; D017886:Durapatite / Q000737:chemistry; D005682:Gadolinium / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry* / Q000378:metabolism; D028581:Lanthanoid Series Elements / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D015394:Molecular Structure
chemical_list: D000577:Amides; C508315:BPAMD ligand; D001672:Biocompatible Materials; D002614:Chelating Agents; D004164:Diphosphonates; D006573:Heterocyclic Compounds, 1-Ring; D028581:Lanthanoid Series Elements; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D017886:Durapatite; D005682:Gadolinium