Improved radiotracing of oxytocin receptor-expressing tumours using the new [111In]-DOTA-Lys8-deamino-vasotocin analogue.

Abstract

Oxytocin receptors (OTR) have been described in a number of tumours of different origin, and represent a new target for specific radiolabelled oxytocin (OT) analogues in cancer diagnosis and therapy. By linking the DOTA chelating agent to position 8 of the deamino derivative of Lys(8)-vasotocin (dLVT), we obtained a new compound (DOTA-dLVT) with the following characteristics: (1) it forms a monomeric and stable compound that binds to OTR with an affinity comparable to that of the endogenous OT ligand; (2) it is characterised by a very good selectivity profile for the human OTR, with a low affinity binding to the closely related V1a, V1b and V2 vasopressin receptor subtypes; (3) it induces rapid and persistent receptor internalisation and (4) when radiolabelled, [(111)In]-DOTA-dLVT is efficiently and selectively taken up by OTR-positive tumours grown in mice. These features makes radiolabelled DOTA-dLVT a very good candidate for the radiotargeting of OTR-expressing tumours.

• Authors: B Chini, M Chinol, P Cassoni, S Papi, A Reversi, L Areces, T Marrocco, G Paganelli, M Manning, G Bussolati
• Journal: British journal of cancer (Br J Cancer) Vol. 89 Issue 5 Pg. 930-6 (Sep 01 2003) ISSN: 0007-0920 [Print] England
• PMID: 12942128 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Chelating Agents
• Heterocyclic Compounds, 1-Ring
• Indium Radioisotopes
• Radioactive Tracers
• Radiopharmaceuticals
• Receptors, Oxytocin
• 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
• Oxytocin
• Vasotocin

Topics

• Animals
• Breast Neoplasms (diagnostic imaging)
• COS Cells
• Carcinoma (diagnostic imaging)
• Chelating Agents (chemistry, pharmacokinetics)
• Glioblastoma (diagnostic imaging)
• Heterocyclic Compounds, 1-Ring (chemistry, pharmacokinetics)
• Humans
• Indium Radioisotopes (pharmacokinetics)
• Isotope Labeling
• Mice
• Neoplasms (diagnostic imaging, metabolism)
• Oxytocin (analogs & derivatives)
• Protein Binding (physiology)
• Radioactive Tracers
• Radioligand Assay (methods)
• Radionuclide Imaging
• Radiopharmaceuticals (chemical synthesis, pharmacokinetics)
• Receptors, Oxytocin (metabolism)
• Sensitivity and Specificity
• Stomach Neoplasms (diagnostic imaging)
• Tissue Distribution
• Transfection
• Tumor Cells, Cultured
• Vasotocin (analogs & derivatives, chemical synthesis, pharmacokinetics)