Areolar-cutaneous junction injections, performed under these conditions, augment SN activity dramatically in most patients. Hotter nodes provide several benefits, especially when next-day surgery is contemplated, and should also reduce the extent of dissection needed to remove the sentinel node.
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.
Gaucher disease (GD) is frequently associated with reduced plasma levels of low density lipoproteins, presumably due to increased catabolism of LDL. The purpose of this study was to determine the distribution of Tc‐99m LDL (Tc‐LDL) in Gaucher patients, and compare the findings to bone marrow distribution. Four patients with non‐neuropathic Gaucher disease (type 1) underwent baseline whole body imaging at 4 and 24 h after injection of dialyzed autologous LDL labeled with 10–20 mCi Tc‐99m‐pertechnetate. Three of the four patients were treated with macrophage‐targeted alglucerase (Ceredase). The LDL studies were compared to concurrent bone marrow scans performed with 10 mCi Tc‐99m sulfur colloid (Tc‐SC). Follow‐up Tc‐LDL and Tc‐SC scans were obtained 12–14 months later. Tc‐LDL activity was abnormally increased in the spleen and long bones of the upper and lower extremities. Liver activity was also increased. Prominent blood pool activity 4 h after injection mostly cleared on the 24‐hour images. The distribution of Tc‐SC was congruent with Tc‐LDL activity. All patients had mild‐to‐moderate hepatomegaly and peripheral bone marrow expansion. One patient had been previously splenectomized and the remaining three had moderate‐to‐severe splenomegaly. Two of the three treated patients showed regression of peripheral bone marrow activity with therapy, along with a comparable decrease in Tc‐LDL uptake. Our study with Tc‐LDL and Tc‐SC suggests that in patients with Gaucher disease native LDL is taken up by the reticuloendothelial system (RES) of the spleen and bone marrow in addition to increased uptake by the liver. This abnormal uptake (presumably by macrophages of the RES) may account for accelerated LDL catabolism and reduced plasma levels of LDL. Serial LDL studies can be performed, allowing for longitudinal follow‐up after drug or enzyme therapies.
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