111In-labeled 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid-lys(8)-vasotocin: a new powerful radioligand for oxytocin receptor-expressing tumors.
We developed a radioactive ligand for tumors expressing oxytocin receptors (OTRs) by linking the chelating agent 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA) to Lys(8)-vasotocin (LVT), an analogue of oxytocin with high affinity for OTRs. The new reagent (DOTA-LVT) retained high affinity for human OTRs, as proved by in vitro affinity binding to cells endogenously expressing OTRs, such as MCF7 breast carcinoma and MOG-U-V-W glioblastoma cells lines, as well as to transiently transfected COS7 cells. In in vivo experiments, DOTA-LVT carrying (111)In showed specific binding activity to OTR-positive TS/A mouse mammary tumors. The present study opens new perspectives for imaging and, possibly, therapy of OTR-positive human tumors such as breast and endometrial carcinomas, neuroblastomas, and glioblastomas.
Bussolati
G
G
Department of Biomedical Sciences and Human Oncology, University of Torino, Vai Santena 7, 10126 Torino, Italy. bussolati@molinette.unito.it
Chinol
M
M
Chini
B
B
Nacca
A
A
Cassoni
P
P
Paganelli
G
G
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism; D019556:COS Cells; D005260:Female; D005909:Glioblastoma / Q000378:metabolism; D019073:HT29 Cells / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000378:metabolism* / Q000493:pharmacokinetics; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D007205:Indium Radioisotopes / Q000737:chemistry*; D007553:Isotope Labeling; D007700:Kinetics; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000378:metabolism* / Q000493:pharmacokinetics; D018045:Receptors, Oxytocin / Q000096:biosynthesis / Q000378:metabolism*; D014018:Tissue Distribution; D014668:Vasotocin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000378:metabolism* / Q000493:pharmacokinetics
C428503:1,4,7,10-tetraazacyclododecane-N,N',N''N'''-etraacetic acid-lys(8)-vasotocin; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; D007205:Indium Radioisotopes; D019275:Radiopharmaceuticals; D018045:Receptors, Oxytocin; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D014668:Vasotocin