title: Lanthanide(III) complexes of bis(phosphonate) monoamide analogues of DOTA: bone-seeking agents for imaging and therapy.
abstract: Lanthanide complexes of DOTA derivatives 2a (BPAMD) and 2b (BPAPD), having a monoamide pendant arm with a bis(phosphonate) moiety, were comparatively tested for application in MRI, radiotherapy, and bone pain palliation. (1)H, (31)P, and (17)O NMR spectroscopy show that they are nine-coordinated, with one water molecule in the first coordination sphere of the Ln(III) ion. The bis(phosphonate) moieties are not coordinated to the lanthanide and predominantly mono- and diprotonated at physiological pH. The parameters governing the longitudinal relaxivities of the Gd complexes are similar to those of other monoamides of DOTA reported in the literature. Upon adsorption on hydroxyapatite, the relaxivities at 20 MHz and 25 degrees C of Gd-2a and Gd-2b were 22.1 and 11 s(-1) mM(-1), respectively. An in vivo gamma-ray imaging study showed that the (177)Lu complexes of 2a and 2b have a high affinity for bones, particularly for growth plates and teeth with a prolonged retention.
authors.affiliation: Biocatalysis and Organic Chemistry, Department of Biotechnology, Delft University of Technology, Julianalaan 136, Delft, The Netherlands.
authors.forename: Tomás
authors.initials: T
authors.lastname: Vitha
authors.forename: Vojtech
authors.initials: V
authors.lastname: Kubícek
authors.forename: Petr
authors.initials: P
authors.lastname: Hermann
authors.forename: Luce Vander
authors.initials: LV
authors.lastname: Elst
authors.forename: Robert N
authors.initials: RN
authors.lastname: Muller
authors.forename: Zvonimir I
authors.initials: ZI
authors.lastname: Kolar
authors.forename: Hubert T
authors.initials: HT
authors.lastname: Wolterbeek
authors.forename: Wouter A P
authors.initials: WA
authors.lastname: Breeman
authors.forename: Ivan
authors.initials: I
authors.lastname: Lukes
authors.forename: Joop A
authors.initials: JA
authors.lastname: Peters
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001842:Bone and Bones / Q000000981:diagnostic imaging*; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D004164:Diphosphonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D005682:Gadolinium; D006573:Heterocyclic Compounds, 1-Ring / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D007811:Lanthanum; D008024:Ligands; D008187:Lutetium; D008297:Male; D011868:Radioisotopes; D011877:Radionuclide Imaging; D051381:Rats; D011917:Rats, Inbred Lew; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: C528502:(4-(((bis(phosphonopropyl))carbamoyl)methyl)-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl)acetic acid; D000577:Amides; C508315:BPAMD ligand; D002614:Chelating Agents; D004164:Diphosphonates; D006573:Heterocyclic Compounds, 1-Ring; D008024:Ligands; D011868:Radioisotopes; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D008187:Lutetium; D007811:Lanthanum; D005682:Gadolinium