A bisphosphonate monoamide analogue of DOTA: a potential agent for bone targeting.
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.
Kubícek
Vojtech
V
Laboratory of Organic Chemistry and Catalysis, Delft University of Technology, Julianalaan 136, 2628 BL Delft, The Netherlands.
Rudovský
Jakub
J
Kotek
Jan
J
Hermann
Petr
P
Vander Elst
Luce
L
Muller
Robert N
RN
Kolar
Zvonimir I
ZI
Wolterbeek
Hubert Th
HT
Peters
Joop A
JA
Lukes
Ivan
I
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
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