Synthesis, characterisation and evaluation of a novel copper-64 complex with selective uptake in EMT-6 cells under hypoxic conditions

Academic Article


  • The radiometal 64Cu is now widely used in the development of diagnostic imaging agents for positron emission tomography (PET). The present study has led to the development and evaluation of a novel chelating agent for 64Cu: the new monothiourea tripodal ligand 1-benzoyl-3-{6-[(bis- pyridin-2-ylmethyl-amino)-methyl]-pyridin-2-yl}-thiourea (MTUBo). X-ray crystallographic analysis has shown this ligand forms a mononuclear complex with copper(ii) and co-ordinates via a trigonal bipyramidal N4S array of donor atoms. Promisingly, cell uptake studies revealed that 64Cu- MTUBo selectively accumulates in EMT-6 cells incubated under hypoxic conditions which may result from its relatively high CuII/I redox potential. Small-animal PET imaging and ex vivo biodistribution studies in EMT-6 tumor bearing BALB/c mice revealed significant tumor uptake after 1 h p.i., yielding tumor-to-muscle (T/M) and tumor-to-blood (T/B) ratios of 8.1 and 1.1, respectively. However, injection of 64Cu-acetate resulted in similar uptake indicating that the observed uptake was most likely non-specific. Despite showing high in vitro stability, it is likely that in vivo the complex undergoes transchelation to proteins within the blood in a relatively short timeframe. For comparison, the hypoxia imaging agent 64Cu-ATSM was also evaluated in the same murine tumor model and showed about 60% higher tumor uptake than 64Cu-MTUBo. © The Royal Society of Chemistry.
  • Digital Object Identifier (doi)

    Author List

  • Knight JC; Wuest M; Saad FA; Wang M; Chapman DW; Jans HS; Lapi SE; Kariuki BM; Amoroso AJ; Wuest F
  • Start Page

  • 12005
  • End Page

  • 12014
  • Volume

  • 42
  • Issue

  • 33