title: Tumour targeting of Auger emitters using DNA ligands conjugated to octreotate.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Peter MacCallum Cancer Centre, Melbourne, Australia. pavel.lobachevsky@petermac.org
authors.forename: Pavel
authors.initials: P
authors.lastname: Lobachevsky
authors.forename: Jai
authors.initials: J
authors.lastname: Smith
authors.forename: Delphine
authors.initials: D
authors.lastname: Denoyer
authors.forename: Colin
authors.initials: C
authors.lastname: Skene
authors.forename: Jonathan
authors.initials: J
authors.lastname: White
authors.forename: Bernard L
authors.initials: BL
authors.lastname: Flynn
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Kerr
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Hicks
authors.forename: Roger F
authors.initials: RF
authors.lastname: Martin
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001692:Biological Transport; D006690:Bisbenzimidazole / Q000737:chemistry; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D004247:DNA / Q000378:metabolism*; D054879:Halogenation; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D007457:Iodine Radioisotopes / Q000378:metabolism; D008024:Ligands; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D015282:Octreotide / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics; D017481:Receptors, Somatostatin / Q000378:metabolism
chemical_list: D007457:Iodine Radioisotopes; D008024:Ligands; D017481:Receptors, Somatostatin; D004247:DNA; C093733:somatostatin receptor 2; D006690:Bisbenzimidazole; D015282:Octreotide