Is [(99m)Tc]glucarate uptake mediated by fructose transporter GLUT-5?

PURPOSE: There is growing interest in the ability of [(99m)Tc]Glucarate ([(99m)Tc]GLA) to accumulate in viable tumor cells. Recent vivo studies suggest that [(99m)Tc]Glucarate could be helpful for tumor detection. Fructose transport is thought to be implicated. It is clearly established that facilitated fructose transport in tumor cells is related to the GLUT-5 transporter. This study therefore investigated whether [(99m)Tc]GLA uptake is mediated by GLUT-5 transporter. METHODS: Different tumor cell lines were used. Modulation of GLUT-5 expression was assessed with and without antisense oligonucleotides directed against GLUT-5. GLUT-5 expression was assessed by indirect cell ELISA. To correlate GLUT-5 expression with tracer accumulation, [(99m)Tc]GLA uptake was determined after antisense treatment. A competition with fructose was also monitored. RESULTS: Inhibition of GLUT-5 expression by antisense oligonucleotides directed against GLUT-5 was effective after 24 h. An optimal of 10µM antisense oligonucleotides directed against GLUT-5 produced a 30%-40% decrease in protein expression. Modulation of [(99m)Tc]GLA uptake was monitored either by use of specific antisense oligonucleotides or by competition with fructose. Both of them produced a significant decrease of [(99m)Tc]GLA accumulation in all tested cell lines. CONCLUSION: Our results clearly demonstrate that [(99m)Tc]GLA uptake is related to GLUT-5 transporter expression and transport. In tumor imaging, [(99m)Tc]GLA may be a useful tool for non-invasive detection of malignant tumors expressing high levels of GLUT-5 transporter as, for example, breast cancers.