title: Silencing of phosphonate-gadolinium magnetic resonance imaging contrast by hydroxyapatite binding.
abstract: OBJECTIVE
  GdDOTP5- is a highly charged, bone-seeking paramagnetic complex that could potentially detect bone lesions by magnetic resonance imaging (MRI). To date, its pharmacokinetics, effects on organ relaxivity, and interaction with hydroxyapatite (HA) has not been described.
  
  
  METHODS
  Liver, kidney, and bone MRI images were obtained on male white rabbits after the administration of GdDOTP5- or a gold standard MRI contrast agent, GdDTPA2-. Parallel in vitro experiments quantified the effect of HA binding on GdDOTP5- -induced changes in relaxivity.
  
  
  RESULTS
  The 2 compounds showed similar MRI enhancements in visceral tissues, but no enhancement of bone was evident with GdDOTP5- despite confirmation of bone and HA binding of the radioactive 153SmDOTP5- and 111InDOTP5- derivatives. In vitro experiments demonstrated that GdDOTP5--induced changes in relaxivity were silenced upon HA binding but could be recovered by acid elution of the complex.
  
  
  CONCLUSIONS
  HA binding assays revealed that GdDOTP5- is essentially MR silent when bound to bone, likely because of the exclusion of all outer sphere water molecules from the surface of the complex. These data suggest a novel strategy for creating highly sensitive, switchable MRI contrast agents.
authors: Department of Radiology, Faculty of Medicine and Hospital Service of Imageology, University of Coimbra, Coimbra, Portugal.
authors: F Caseiro
authors: FC
authors: Alves
authors: Paulo
authors: P
authors: Donato
authors: A Dean
authors: AD
authors: Sherry
authors: Atif
authors: A
authors: Zaheer
authors: Shanrong
authors: S
authors: Zhang
authors: Angelo Josue M
authors: AJ
authors: Lubag
authors: Matthew E
authors: ME
authors: Merritt
authors: Robert E
authors: RE
authors: Lenkinski
authors: John V
authors: JV
authors: Frangioni
authors: Maria
authors: M
authors: Neves
authors: M Isabel M
authors: MI
authors: Prata
authors: A C
authors: AC
authors: Santos
authors: João J P
authors: JJ
authors: de Lima
authors: Carlos F G C
authors: CF
authors: Geraldes
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D005682:Gadolinium / Q000493:pharmacokinetics*; D019786:Gadolinium DTPA / Q000493:pharmacokinetics*; D006882:Hydroxyapatites / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D009942:Organometallic Compounds / Q000493:pharmacokinetics; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D006882:Hydroxyapatites; D009942:Organometallic Compounds; D005682:Gadolinium; D019786:Gadolinium DTPA