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


CONCLUSIONS
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.
Laboratory of Biophysics, IFRESIS Faculty of Medicine University of Saint Etienne-Lyon, France 42023. vanina.isnardi@lyon.unicancer.fr
Vanina
V
Isnardi
Anthony
A
Clotagatide
Sebastien
S
Bruel
Nathalie
N
Perek
D001692:Biological Transport / Q000187:drug effects; D045744:Cell Line, Tumor; D005632:Fructose / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D005937:Glucaric Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D051296:Glucose Transporter Type 5 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000235:genetics; D015609:Organotechnetium Compounds / Q000378:metabolism*
D051296:Glucose Transporter Type 5; D016376:Oligonucleotides, Antisense; D015609:Organotechnetium Compounds; C067171:technetium Tc 99m glucarate; D005632:Fructose; D005937:Glucaric Acid