Tuning glutamine binding modes in Gd-DOTA-based probes for an improved MRI visualization of tumor cells.
Three new magnetic resonance imaging probes that target glutamine transporters have been synthesized. They consist of a Gd-DOTA-monoamide moiety (DOTA=1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) linked through a six carbon atom chain to a vector represented by a glutamine residue bound through alpha-carboxylic, gamma-carboxamidic, or alpha-amino functionalities. Their uptake by HTC (rat hepatocarcinoma) and healthy rat hepatocytes has shown that the system containing the glutamine vector bound through the alpha-carboxylic group displays a markedly higher affinity for tumor cells. The observed behavior is rationalized in terms of the exploitation of an additional glutamine transporter active in hepatic tumor cells.
Stefania
Rachele
R
Dipartmento di Chimica IFM and Molecular Imaging Center, Università di Torino, Via Nizza 52, 10125 Torino, Italy.
Tei
Lorenzo
L
Barge
Alessandro
A
Geninatti Crich
Simonetta
S
Szabo
Ibolya
I
Cabella
Claudia
C
Cravotto
Giancarlo
G
Aime
Silvio
S
D000818:Animals; D003287:Contrast Media / Q000737:chemistry*; D003500:Cyclization; D005973:Glutamine / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D009369:Neoplasms / Q000175:diagnosis*; D009942:Organometallic Compounds / Q000737:chemistry*; D051381:Rats; D014407:Tumor Cells, Cultured
D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D005973:Glutamine; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate