Section 57
Chapter 56,708

Tumour targeting of Auger emitters using DNA ligands conjugated to octreotate

Lobachevsky, P.; Smith, J.; Denoyer, D.; Skene, C.; White, J.; Flynn, B.L.; Kerr, D.J.; Hicks, R.J.; Martin, R.F.

International Journal of Radiation Biology 88(12): 1009-1018


ISSN/ISBN: 1362-3095
PMID: 22372657
DOI: 10.3109/09553002.2012.666375
Accession: 056707389

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.

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