67Ga-transferrin and 67Ga-lactoferrin binding to tumor cells: specific versus nonspecific glycoprotein-cell interaction.
In order to evaluate the mechanisms which facilitate the transfer of 67Ga from transferrin in plasma to intracellular binding sites, lactoferrin, a glycoprotein with high affinity for 67Ga, was used as a probe to study the effect of protein binding on gallium uptake by tumor cells. The in vivo effect of transferrin and lactoferrin on the biodistribution of 67Ga was studied in nude mice bearing human malignant mesothelioma. Tumor uptake of 67Ga was reduced 30% by transferrin and 57% by lactoferrin compared with 67Ga-citrate alone. Liver uptake of 67Ga, however, was significantly increased by binding to lactoferrin. The in vitro binding of 67Ga to tumor cells (Burkitt's lymphoma) was apparently promoted by the addition of transferrin or lactoferrin to the incubation medium, but this glycoprotein enhancement of gallium uptake by the cells was dependent on the albumin level, decreasing in absolute uptake as the albumin concentration was increased, suggesting nonspecific binding of glycoproteins to cells. Because of the significant amount of nonspecific binding of 67Ga-labeled glycoprotein complexes in cell culture experiments, in vitro experiments should be used with caution in developing a hypothesis on the mechanisms of cellular uptake of radiogallium. In vivo experiments suggest different mechanisms for cellular uptake of 67Ga in neoplastic tissue and in liver.
D000328:Adult; D000418:Albumins / Q000378:metabolism; D000818:Animals; D002051:Burkitt Lymphoma / Q000378:metabolism*; D005710:Gallium Radioisotopes / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007781:Lactoferrin / Q000378:metabolism*; D007782:Lactoglobulins / Q000378:metabolism*; D008297:Male; D008654:Mesothelioma / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000378:metabolism; D010997:Pleural Neoplasms / Q000378:metabolism*; D011485:Protein Binding; D014168:Transferrin / Q000378:metabolism*
D000418:Albumins; D005710:Gallium Radioisotopes; D006023:Glycoproteins; D007782:Lactoglobulins; D014168:Transferrin; D007781:Lactoferrin