Tumour targeting of Auger emitters using DNA ligands conjugated to octreotate Conference Paper uri icon


  • The objective of the study was to conjugate the DNA binding ligand para-[(125)I]-iodoHoechst to octreotate, and to explore the tumour targeting potential of this conjugate in the octreotate-somatostatin receptor system.We synthesized a Hoechst analogue containing a tri-butylstannyl group in the para position of phenyl ring, conjugated it to the N-terminal amino group of octreotate and prepared (125)I-labelled conjugate by iododestannylation. We used the somatostatin receptor (SSTR2) over-expressing cell line A427-7 derived from its parent A427 human non-small cell lung carcinoma cell line to investigate SSTR2 affinity and receptor-mediated internalisation of the conjugate, and the mouse A427-7 tumour xenograft model for in vivo biodistribution studies of the radiolabelled conjugate.A method was developed for convenient preparation of high specific activity radioiodinated conjugate which retains affinity for somatostatin receptors and is internalised into A427-7 SSTR2 over-expressing cells via a receptor-mediated mechanism. The conjugate accumulates in mouse A427-7 tumour xenografts following intravenous administration.A dual targeting strategy for Auger endoradiotherapy, in which a DNA ligand is used to target the Auger decay to DNA, in conjunction with receptor-mediated targeting to specific receptors, using a labelled DNA ligand/peptide conjugate, has been demonstrated for the octreotate-somatostatin receptor system.


  • Lobachevsky, Pavel
  • Smith, Jai
  • Denoyer, Delphine
  • Skene, Colin
  • White, Jonathan
  • Flynn, Bernard L
  • Kerr, Daniel J
  • Hicks, Rodney J
  • Martin, Roger F

publication date

  • December 2012