Tumour targeting of Auger emitters using DNA ligands conjugated to octreotate

Pavel N Lobachevsky, Jai Smith, Delphine Denoyer, Colin Edward Skene, Jonathan Michael White, Bernard Luke Flynn, Daniel Jarrah Kerr, Rodney Hicks, Roger F Martin

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9 Citations (Scopus)


Purpose: The objective of the study was to conjugate the DNA binding ligand para-[125I]-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 125I-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. ? 2012 Informa UK, Ltd.
Original languageEnglish
Pages (from-to)1009 - 1018
Number of pages10
JournalInternational Journal of Radiation Biology
Issue number12
Publication statusPublished - 2012

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