Background. Breast cancers have higher than normal glucose metabolism, but the mechanism of glucose entry into these tumors is not well understood. Methods. The expression of five facilitative glucose transporters, Glut‐1 (erythrocyte type), Glut‐2 (liver type), Glut‐3 (brain type), Glut‐4 (muscle/fat type), and Glut‐5 (small intestine type), was studied by immunohistochemistry of paraffin sections from 12 primary human breast cancers and 8 lymph node metastases from 2 patients. Rat tissues known to express these glucose transporters were used as controls. Results. All the primary breast cancers and the lymph node metastases were positive for Glut‐1. This transporter was expressed on the cell membrane and in the cytoplasm of the tumor cells, but exhibited marked intratumoral and intertumoral variability in the proportions of positive cells and the intensity of staining. Staining of the normal mammary epithelium, if present, was much lower than observed in tumor cells from the same patient. Glut‐2 was expressed in all of the tumors, but the intensity of staining was not consistently stronger than that seen in healthy breast. Clusters of Glut‐4‐positive granule were observed in cells in six of the tumors. None of the tumors or the healthy breast in the tissues studied expressed Glut‐3 or Glut‐5. Conclusions. Higher expression of the glucose transporter Glut‐1 by breast cancer cells compared with the healthy breast tissue is common. Increased glucose transporter protein expression may contribute to the increased uptake of 2‐[18F]‐fluoro‐2‐deoxy‐D‐glucose (FDG) by these tumors observed by positron emission tomography (PET) imaging.

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The purpose of this study was to evaluate the localization of positron emission tomography (PET) tracers [2-deoxy-2-fluoro-D-glucose (FDG), thymidine, and L-methionine] in sites of bacterial infection, and to contrast this with that of other tracers. The left calf muscles of rats were infected with a suspension of Escherichia coli and the biodistribution of 18F- or 3H-FDG, 3H-thymidine, L-11C- or 3H-methionine, gallium-67 citrate (67Ga-citrate) and iodine-125 human serum albumin (125I-HSA) was determined in these animals. 3H-FDG uptake in the infectious foci was evaluated by autoradiography of histological sections. Although 18F-FDG, 67Ga-citrate, and 125I-HSA showed comparatively high uptake in the infected muscle [the percentage activity of injected dose (ID) per gram of tissue normalized for rat weight in kilogram (%ID/g)xkg at 2 h postinjection was as follows: 18F-FDG, 0.184+/-0.026 to 0.218+/-0.046; 67Ga-citrate, 0.221+/-0.016; 125I-HSA, 0. 198+/-0.019], the infected muscle to blood ratio was much higher for 18F-FDG than for 67Ga-citrate or 125I-HSA (18F-FDG, 10.31+/-0.76 to 14.89+/-2.26; 67Ga-citrate, 1.24+/-0.67; 125I-HSA, 0.20+/-0.02). The draining reactive lymph nodes also showed higher accumulation of 18F-FDG than of 67Ga-citrate or 125I-HSA. The uptake of 3H-thymidine and L-11C- or 3H-methionine in the infected muscle was lower than that of 18F- or 3H-FDG (at 2 h postinjection, 3H-thymidine = 0. 039+/-0.005 and L-3H-methionine = 0.063+/-0.007 (%ID/g)xkg. Autoradiographs showed that the highest 3H-FDG uptake was seen in the area of inflammatory cell infiltration surrounding the necrotic region. In conclusion, 18F-FDG, which rapidly accumulates in sites of bacterial infection and in reactive lymph nodes with a high target to background ratio, appears to be a promising infection detection agent.

Secretion of anionic endo-and xenobiotics is essential for the survival of animal and plant cells; however, the underlying molecular mechanisms remain uncertain. To better understand one such model system-i.e., secretion of bile acids by the liver-we utilized a strategy analogous to that employed to identify the multidrug resistance (mdr) genes. We synthesized the methyl ester of glycocholic acid (GCE), which readily enters cells, where it is hydrolyzed to yield glycocholic acid, a naturally occurring bile acid. The rat hepatomaderived HTC cell line gradually acquired resistance to GCE concentrations 20-fold higher than those which inhibited growth of naive cells, yet intracellular accumulation of radio-

Recent studies on the intraperitoneal administration of radiolabeled monoclonal antibodies indicate that the diaphragm and, in particular, the lymphatics associated with the diaphragm are more involved in the transport of such high-molecular-mass moieties than was earlier suspected. The current study examines the role of the diaphragm in the i.p. transport of an IgG2a murine monoclonal antibody, 5G6.4, by observing the effect on the absorption of the antibody produced when the diaphragm has been scarred. Normal, sham-operated, and diaphragmatically scarred (abrasions made with 600-grade sandpaper) female Sprague Dawley rats (150-250 g) were administered intraperitoneal injections of 125labeled 5G6.4 in a volume of 2.0 cm3. Approximately 5 micrograms antibody protein was administered in the individual 19-microCi injections per rat. Scarring was effective in partially blocking the amount of labeled antibody that crossed the diaphragm. Mean diaphragm levels (% injected dose/g) of 125I-labeled 5G6.4 from the scarred group were 16.8% lower than values from the sham-operated rats and 37.2% lower than those from the control rats. The blockade was effective in slowing the appearance of the labeled antibody in the systemic circulation. The half-time to absorption was significantly prolonged in the scarred group; mean t1/2 absorption values of 2.5 h for the control group, 5.3 h for the sham-operated group, and 9.6 h for the diaphragmatically blocked group were recorded. Scarring the diaphragm reduced the mean maximum blood concentration by 27.6% over the control group and 23.9% over the sham-operated group. The mean time to maximum blood concentration was lengthened by 93..0% over the control group and 35.3% over the sham-operated group due as a result of scarification. Presumably this impedence to absorption would increase the time that the radiolabeled antibody bathed the peritoneal space. The scarred group also had the largest "system mean residence time" (162.5 h) compared to the sham-operated (147.9 h) and control (118.7 h) groups. These values further verify the effect of surgery on the kinetics of the i.p. administered radiolabeled monoclonals. This work demonstrates that scarifying the diaphragm does alter the kinetics of the i.p. administered monoclonal antibodies and supports the concept that transdiaphragmatic lymphatic absorption is an important route of antibody clearance from the peritoneal cavity.