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

F. Caseiro Alves, Paulo Donato, A. Dean Sherry, Atif Zaheer, Shanrong Zhang, Angelo Josue M Lubag, Matthew E. Merritt, Robert E. Lenkinski, John V. Frangioni, Maria Neves, M. Isabel M Prata, A. C. Santos, João J P De Lima, Carlos F G C Geraldes

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Rationale and Objectives: 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 GdDOTP 5- 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.

Original languageEnglish (US)
Pages (from-to)750-760
Number of pages11
JournalInvestigative Radiology
Volume38
Issue number12
DOIs
StatePublished - Dec 1 2003

    Fingerprint

Keywords

  • Gadolinium complexes
  • Hydroxyapatite
  • MRI contrast agents
  • Magnetic resonance imaging
  • Phosphonates

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Caseiro Alves, F., Donato, P., Sherry, A. D., Zaheer, A., Zhang, S., Lubag, A. J. M., Merritt, M. E., Lenkinski, R. E., Frangioni, J. V., Neves, M., Prata, M. I. M., Santos, A. C., De Lima, J. J. P., & Geraldes, C. F. G. C. (2003). Silencing of Phosphonate-Gadolinium Magnetic Resonance Imaging Contrast by Hydroxyapatite Binding. Investigative Radiology, 38(12), 750-760. https://doi.org/10.1097/01.rli.0000084891.15996.0f