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-DOTAmonoamide 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 acarboxylic, g-carboxamidic, or a-amino functionalities. Their uptake by HTC (rat hepatocarcinoma) and healthy rat hepatocytes has shown that the system containing the glutamine vector bound through the a-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.