title: In vitro and in vivo magnetic resonance detection of tumor cells by targeting glutamine transporters with Gd-based probes.
abstract: The glutamine transporting system is up-regulated in tumor cells because cell proliferation requires the uptake of large quantities of glutamine. It has been found that the paramagnetic magnetic resonance imaging (MRI) reporter Gd-DOTAMA-C6-Gln, where the glutamine residue is covalently bound to the Gd chelate through a C6 spacer, accumulates in tumor cells both "in vitro" and "in vivo" experiments. The observation that the relaxivity of cellular pellets does not increase with the increase in the amounts of entrapped Gd chelate is taken as an indication that the internalization has occurred through receptor mediated endocytosis. The iv administration of Gd-DOTAMA-C6-Gln allowed the MRI visualization of tumor masses in A/J mice grafted with the murine neuroblastoma cell line Neuro-2a and in Her-2/neu transgenic mice developing multiple mammary carcinoma, respectively.
authors.affiliation: Department of Chemistry I.F.M, University of Torino, Via P. Giuria 7, Torino, 10125, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Geninatti Crich
authors.forename: Claudia
authors.initials: C
authors.lastname: Cabella
authors.forename: Alessandro
authors.initials: A
authors.lastname: Barge
authors.forename: Simona
authors.initials: S
authors.lastname: Belfiore
authors.forename: Cristina
authors.initials: C
authors.lastname: Ghirelli
authors.forename: Luciano
authors.initials: L
authors.lastname: Lattuada
authors.forename: Stefania
authors.initials: S
authors.lastname: Lanzardo
authors.forename: Armando
authors.initials: A
authors.lastname: Mortillaro
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Tei
authors.forename: Massimo
authors.initials: M
authors.lastname: Visigalli
authors.forename: Guido
authors.initials: G
authors.lastname: Forni
authors.forename: Silvio
authors.initials: S
authors.lastname: Aime
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000138:chemical synthesis; D003287:Contrast Media / Q000493:pharmacokinetics; D005260:Female; D005682:Gadolinium; D005973:Glutamine / Q000378:metabolism*; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D008279:Magnetic Resonance Imaging; D008325:Mammary Neoplasms, Experimental / Q000175:diagnosis / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000175:diagnosis* / Q000473:pathology; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D014183:Transplantation, Heterologous
chemical_list: D002352:Carrier Proteins; D002614:Chelating Agents; D003287:Contrast Media; D005682:Gadolinium; D005973:Glutamine; D006573:Heterocyclic Compounds, 1-Ring; D009942:Organometallic Compounds; D018719:Erb-b2 Receptor Tyrosine Kinases; C037853:glutamine transport proteins; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid