Silencing of phosphonate-gadolinium magnetic resonance imaging contrast by hydroxyapatite binding.
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.
Alves
F Caseiro
FC
Department of Radiology, Faculty of Medicine and Hospital Service of Imageology, University of Coimbra, Coimbra, Portugal.
Donato
Paulo
P
Sherry
A Dean
AD
Zaheer
Atif
A
Zhang
Shanrong
S
Lubag
Angelo Josue M
AJ
Merritt
Matthew E
ME
Lenkinski
Robert E
RE
Frangioni
John V
JV
Neves
Maria
M
Prata
M Isabel M
MI
Santos
A C
AC
de Lima
João J P
JJ
Geraldes
Carlos F G C
CF
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
D006882:Hydroxyapatites; D009942:Organometallic Compounds; D005682:Gadolinium; D019786:Gadolinium DTPA