An osteoclast-targeting agent for imaging and therapy of bone metastasis

Bioorg Med Chem Lett. 2008 Sep 1;18(17):4789-93. doi: 10.1016/j.bmcl.2008.07.092. Epub 2008 Jul 27.

Abstract

A hybrid compound (DO3A-BP) featuring a radiometal bifunctional chelator (1,4,7,10-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid, DOTA) and an osteoclast-targeting moiety (bisphosphonate) was designed and synthesized. The (111)In-labeled complex of DO3A-BP showed significantly elevated uptake in osteoclasts compared to the undifferentiated adherent bone marrow derived cells. Biodistribution studies revealed a favorable tissue distribution profile in normal mice with high bone uptake and long retention, and low or negligible accumulation in non-target organs.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bone Neoplasms / diagnostic imaging*
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / secondary
  • Cells, Cultured
  • Diagnostic Imaging*
  • Diphosphonates / chemistry
  • Diphosphonates / pharmacokinetics
  • Diphosphonates / pharmacology*
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Heterocyclic Compounds, 1-Ring / pharmacokinetics
  • Heterocyclic Compounds, 1-Ring / pharmacology*
  • Indium Radioisotopes
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Osteoclasts / metabolism*
  • Radionuclide Imaging

Substances

  • 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid
  • Diphosphonates
  • Heterocyclic Compounds, 1-Ring
  • Indium Radioisotopes
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid