Tumour targeting of Auger emitters using DNA ligands conjugated to octreotate

Int J Radiat Biol. 2012 Dec;88(12):1009-18.
Lobachevsky P, Smith J, Denoyer D, Skene C, White J, Flynn BL, Kerr DJ, Hicks RJ, Martin RF.
Int J Radiat Biol. 2012 Dec;88(12):1009-18.
Coniugare il DNA ligante (125)Iodio ad octreotide ed esplorarne le potenzialità di monitoraggio tumorale nel sistema recettoriale octreotide-somatostatina.
DNA ligante (125)Iodio-octreotide/monitoraggio tumorale.

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.