Biodistribution of neoglycoproteins in mice bearing solid Ehrlich tumor.
Synthetic neoglycoproteins were employed for the specific detection of their corresponding cellular sugar receptors, such as endogenous lectins, by specific protein-carbohydrate interaction. A panel of 16 radioiodinated probes with defined carbohydrate content, attached to the carrier protein bovine serum albumin, disclosed marked differences in the expression of corresponding sugar receptors on Ehrlich ascites tumor cells in vitro as an exemplary tumor model. To quantify tumor uptake in the more complex in vivo situation and to assess binding to individual organs attributable to the various types of carbohydrates we determined the biodistribution of the radiolabelled neoglycoproteins 48 h after injection into tumor-bearing mice. The individual pattern of retention of radioactivity demonstrated distinct properties of the different organs that need to be accounted for in drug-targeting and tumor-imaging studies, based on protein-carbohydrate interactions. Combined tumor-to-blood and tumor-to-muscle ratios of neoglycoprotein accumulation were well above 1 after covalent attachment of xylose or glucuronic acid, respectively, to the carrier protein. These data constitute the basis for further refinements of the carbohydrate part of suitable neoglycoproteins to allow a potentially rational application of neoglycoproteins as drug-targeting vehicles and tumor-imaging radiopharmaceuticals.
Kojima
S
S
Department of Radiopharmacy, School of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Gabius
H J
HJ
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism*; D006023:Glycoproteins / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D006023:Glycoproteins