Silencing of Phosphonate-Gadolinium Magnetic Resonance Imaging Contrast by Hydroxyapatite Binding

RATIONALE AND OBJECTIVES:GdDOTP 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 GdDOTP or a gold standard MRI contrast agent, GdDTPA. Parallel in vitro experiments quantified the effect of HA binding on GdDOTP -induced changes in relaxivity. RESULTS:The 2 compounds showed similar MRI enhancements in visceral tissues, but no enhancement of bone was evident with GdDOTP despite confirmation of bone and HA binding of the radioactive SmDOTP and InDOTP derivatives. In vitro experiments demonstrated that GdDOTP-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 GdDOTP 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.