67Ga-transferrin and 67Ga-lactoferrin binding to tumor cells: Specific versus nonspecific glycoprotein-cell interaction

Abstract

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.

Transferrin Is Not Involved in the Entry of 67Ga into Hepatocytes from Regenerating Liver of Partially Hepatectomized Rats.

“…12) Vallabhajosula et al reported that the uptake of 67 Ga by tumors was reduced by Tf, as compared with 67 Ga-citrate alone, i.e., the uptake of 67 Ga by tumors occurred in an unbound form. 20) Kumagai et al reported that Tf receptors increased in hepatocytes during rat liver regeneration. 21) There is, however, no report concerning the involvement of Tf in the 67 Ga uptake by regenerating liver after partial hepatectomy.…”

Mechanisms of arterial thrombosis in nonparallel streamlines: platelet thrombi grow on the apex of stenotic severely injured vessel wall. Experimental study in the pig model.

“…After overnight fasting blood was withdrawn and platelets were labeled with ["'Indium]tropolone (300-400 ,tCi) as we have previously described (9,10). 18-24 h later the pigs were sedated with a mixture of ketamine and xylazine (Ketalar, Rompun) given intramuscularly, then intubated and ventilated with a Harvard respirator and anesthetized intravenously with sodium pentobarbital (Fort Dodge Lab., Fort Dodge, IA) with the minimal effective dose as previously described (4).…”

“…Autologous platelets were labeled with ["'In]tropolone according to our previously described technique (9). Platelets deposited on the perfused substrate (X 106/cm2) were determined by gamma well counting of the perfused matrix and normalized by blood activity (counts), platelet counts in blood, and surface area (1)(2)(3)(4).…”

Brain tumor protein synthesis and histological grades: A study by positron emission tomography (PET) with C11-L-Methionine

“…In the second step of the examination, regional cerebral blood volume (rCBV) was measured by scanning 12 hours later the patient in the same position under the tomograph but after a non saturating intravenous injection of 2 to 4 mCi of 68 GaC13 (25,26) just eluted from a generator (27,28). One ten minutes scan was taken ten minutes after injection to allow equilibrium of the tracer in the body.…”