In vitro and in vivo magnetic resonance detection of tumor cells by targeting glutamine transporters with Gd-based probes.
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.
Geninatti Crich
Simonetta
S
Department of Chemistry I.F.M, University of Torino, Via P. Giuria 7, Torino, 10125, Italy.
Cabella
Claudia
C
Barge
Alessandro
A
Belfiore
Simona
S
Ghirelli
Cristina
C
Lattuada
Luciano
L
Lanzardo
Stefania
S
Mortillaro
Armando
A
Tei
Lorenzo
L
Visigalli
Massimo
M
Forni
Guido
G
Aime
Silvio
S
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
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