title: Targeting of glucose transport proteins for tumor imaging: is it feasible?
abstract: If glucose transport proteins (Glut) are elevated in tumors they may be good targets for tumor imaging. For targeting, the overexpression of Glut should be a general characteristic of tumors. Moreover agents which bind to Glut should accumulate selectively in tumors.
  
  
  METHODS
  To test this, we quantitated Glut in isolated membranes from three human tumor xenografts, two murine tumor models and normal murine tissues using direct binding studies. Additionally, the biodistribution of two compounds which bind to Glut, 7-[[(2-(3-(125I-p-hydroxyphenyl)propionyl)aminoethyl)amino]carbonyl]-7-+ ++desacetyl-forskolin([125I]HPP forskolin) and [3H]cytochalasin B, were studied in a tumor model which overexpressed Glut.
  
  
  RESULTS
  There were multiple classes of binding sites for [3H]cytochalasin B and a percentage of these sites were competitive with D-glucose but not L-glucose. The rank potency and IC50 values for [3H]cytochalasin B binding were: 2-deoxy-D-glucose (4.5 mM) > or = D-glucose (7 mM) > mannose (25 mM) > galactose (35 mM) > rhamnose (1-3 mM) > sorbitol (1-3 mM) and were similar to reported values for transport. The average density of Glut in four tumor models and normal tissues was between 0.7 and 4 pmole/mg protein, but Kd values were not significantly different (69 nM). In LX-1 human lung tumor xenograft (LX-1) Glut were 10-to-20-fold higher than other tissues (21.6 +/- 0.6 pmole/mg protein, p<0.01). Immunostaining of Glut-1 was more prominent in LX-1 than other xenograft tumors, consistent with the binding data. Glut density was highest in poorly vascularized regions suggesting that Glut upregulation was related to a biofeedback mediated event. Iodine-125 HPP-forskolin and [3H]cytochalasin B did not localize in LX-1 tumors.
  
  
  CONCLUSIONS
  Glut overexpression was not a common characteristic of the five tumors tested. Iodine-125 HPP-forskolin and [3H]cytochalasin B did not localize in LX-1 tumors, indicating that these agents did not target tumors with upregulated Glut. Results suggest that Glut are not a promising target for tumor imaging.
authors.affiliation: DuPont Merck Pharmaceutical Company, North Billerica, Massachusetts, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Nelson
authors.forename: Q J
authors.initials: QJ
authors.lastname: Wang
authors.forename: J P
authors.initials: JP
authors.lastname: Bourque
authors.forename: P D
authors.initials: PD
authors.lastname: Crane
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D005576:Colforsin; D003571:Cytochalasin B; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D051379:Mice; D008819:Mice, Nude; D009004:Monosaccharide Transport Proteins / Q000032:analysis*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000175:diagnosis* / Q000378:metabolism*; D014316:Tritium; D014407:Tumor Cells, Cultured
chemical_list: D007457:Iodine Radioisotopes; D009004:Monosaccharide Transport Proteins; D014316:Tritium; D005576:Colforsin; D003571:Cytochalasin B