Gadolinium Tagged Osteoprotegerin-Mimicking Peptide: A Novel Magnetic Resonance Imaging Biospecific Contrast Agent for the Inhibition of Osteoclastogenesis and Osteoclast Activity

Lubinda Mbundi, Steve Meikle, Rosa Busquets Santacana, Nicholas G. Dowell, Mara Cercignani, Matteo Santin

Research output: Contribution to journalArticle

Abstract

The control of osteoblast/osteoclast cross-talk is crucial in the bone remodelling process
and provides a target mechanism in the development of drugs for bone metabolic diseases.
Osteoprotegerin is a key molecule in this biosignalling pathway as it inhibits osteoclastogenesis
and osteoclast activation to prevent run-away bone resorption. This work reports the synthesis of a
known osteoprotegerin peptide analogue, YCEIEFCYLIR (OP3-4), and its tagging with a gadolinium
chelate, a standard contrast agent for magnetic resonance imaging. The resulting contrast agent
allows the simultaneous imaging and treatment of metabolic bone diseases. The gadolinium-tagged
peptide was successfully synthesised, showing unaltered magnetic resonance imaging contrast
agent properties, a lack of cytotoxicity, and dose-dependent inhibition of osteoclastogenesis in vitro.
These findings pave the way toward the development of biospecific and bioactive contrast agents
for the early diagnosis, treatment, and follow up of metabolic bone diseases such as osteoporosis
and osteosarcoma.
Original languageEnglish
Pages (from-to)1-15
Number of pages15
JournalNanomaterials
Volume8
Issue number6
DOIs
Publication statusPublished - 2 Jun 2018

Keywords

  • osteoporosis
  • magnetic resonance imaging
  • contrast agents

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