Improved radiotracing of oxytocin receptor-expressing tumours using the new [111In]-DOTA-Lys8-deamino-vasotocin analogue.
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.
Chini
B
B
CNR Institute of Neuroscience, Cellular and Molecular Pharmacology Section, Via Vanvitelli 32, 20129 Milano, Italy.
Chinol
M
M
Cassoni
P
P
Papi
S
S
Reversi
A
A
Areces
L
L
Marrocco
T
T
Paganelli
G
G
Manning
M
M
Bussolati
G
G
D000818:Animals; D001943:Breast Neoplasms / Q000000981:diagnostic imaging; D019556:COS Cells; D002277:Carcinoma / Q000000981:diagnostic imaging; D002614:Chelating Agents / Q000737:chemistry / Q000493:pharmacokinetics; D005909:Glioblastoma / Q000000981:diagnostic imaging; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D007553:Isotope Labeling; D051379:Mice; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism; D010121:Oxytocin / Q000031:analogs & derivatives; D011485:Protein Binding / Q000502:physiology; D011849:Radioactive Tracers; D011869:Radioligand Assay / Q000379:methods*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D018045:Receptors, Oxytocin / Q000378:metabolism*; D012680:Sensitivity and Specificity; D013274:Stomach Neoplasms / Q000000981:diagnostic imaging; D014018:Tissue Distribution; D014162:Transfection; D014407:Tumor Cells, Cultured; D014668:Vasotocin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000493:pharmacokinetics*
D002614:Chelating Agents; D006573:Heterocyclic Compounds, 1-Ring; D007205:Indium Radioisotopes; D011849:Radioactive Tracers; D019275:Radiopharmaceuticals; D018045:Receptors, Oxytocin; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D010121:Oxytocin; D014668:Vasotocin