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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Breast Neoplasms / diagnostic imaging
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COS Cells
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Carcinoma / diagnostic imaging
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Chelating Agents / chemistry
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Chelating Agents / pharmacokinetics
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Glioblastoma / diagnostic imaging
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Heterocyclic Compounds, 1-Ring / chemistry
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Heterocyclic Compounds, 1-Ring / pharmacokinetics
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Humans
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Indium Radioisotopes* / pharmacokinetics
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Isotope Labeling
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Mice
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Neoplasms / diagnostic imaging
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Neoplasms / metabolism
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Oxytocin / analogs & derivatives
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Protein Binding / physiology
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Radioactive Tracers*
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Radioligand Assay / methods*
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Radionuclide Imaging
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Radiopharmaceuticals / chemical synthesis*
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Radiopharmaceuticals / pharmacokinetics
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Receptors, Oxytocin / metabolism*
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Sensitivity and Specificity
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Stomach Neoplasms / diagnostic imaging
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Tissue Distribution
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Transfection
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Tumor Cells, Cultured
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Vasotocin / analogs & derivatives*
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Vasotocin / chemical synthesis*
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Vasotocin / pharmacokinetics*
Substances
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Chelating Agents
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Heterocyclic Compounds, 1-Ring
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Indium Radioisotopes
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Radioactive Tracers
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Radiopharmaceuticals
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Receptors, Oxytocin
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1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
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Oxytocin
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Vasotocin