title: Fluorescent fructose derivatives for imaging breast cancer cells.
abstract: Breast cancer cells are known to overexpress Glut5, a sugar transporter responsible for the transfer of fructose across the cell membrane. Since Glut5 transporter is not significantly expressed in normal breast cells, fructose uptake can potentially be used to differentiate between normal and cancerous cells. Fructose was labeled with two fluorophores at the C-1 position: 7-nitro-1,2,3-benzadiazole (NBD) and Cy5.5. The labeling site was chosen on the basis of the presence and substrate specificity of the key proteins involved in the first steps of fructose metabolism. Using fluorescence microscopy, the uptake of the probes was studied in three breast cancer cell lines: MCF 7, MDA-MB-435, and MDA-MB-231. Both fluorescent fructose derivatives showed a very good uptake in all tested cell lines. The level of uptake was comparable to that of the corresponding glucose analogs, 2-NBDG and Cy5.5-DG. Significant uptake of 1-NBDF derivative was not observed in cells lacking Glut5 transporter, while the uptake of the 1-Cy5.5-DF derivative was independent of the presence of a fructose-specific transporter. While 1-NBDF showed Glut5-specific accumulation, the coupling of a large fluorophore such as Cy5.5 likely introduces big structural and electronic changes, leading to a fructose derivative that does not accurately describe the uptake of fructose in cells.
authors: Molecular Imaging Program at Stanford, Department of Radiology, Stanford University, Stanford, California 94305, USA.
authors: Jelena
authors: J
authors: Levi
authors: Zhen
authors: Z
authors: Cheng
authors: Olivier
authors: O
authors: Gheysens
authors: Manish
authors: M
authors: Patel
authors: Carmel T
authors: CT
authors: Chan
authors: Yingbing
authors: Y
authors: Wang
authors: Mohammad
authors: M
authors: Namavari
authors: Sanjiv Sam
authors: SS
authors: Gambhir
mesh_terms: D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives* / Q000032:analysis / Q000138:chemical synthesis / Q000378:metabolism; D001393:Azoles / Q000737:chemistry; D001692:Biological Transport; D001943:Breast Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000648:ultrastructure; D002232:Carbocyanines / Q000032:analysis* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D005260:Female; D005456:Fluorescent Dyes / Q000032:analysis* / Q000138:chemical synthesis / Q000378:metabolism; D005632:Fructose / Q000031:analogs & derivatives* / Q000032:analysis / Q000138:chemical synthesis / Q000378:metabolism; D051296:Glucose Transporter Type 5 / Q000378:metabolism*; D006801:Humans; D008856:Microscopy, Fluorescence; D009578:Nitrobenzenes / Q000737:chemistry; D014407:Tumor Cells, Cultured
chemical_list: C522247:1-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-1-deoxyfructose; C522248:1-Cy5.5-1-deoxyfructose; C510797:7-nitrobenz-2-oxa-1,3-diazol-4-yl; D001393:Azoles; C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D005456:Fluorescent Dyes; D051296:Glucose Transporter Type 5; D009578:Nitrobenzenes; D005632:Fructose; D009327:4-Chloro-7-nitrobenzofurazan