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The function of the reticuloendothelial system (RES) was evaluated after the inoculation of an experimental tumor in rats. Four groups were studied according to tumor size and site. Reticuloendothelial function was evaluated by measuring the biokinetics of a standardized [99Tcm]-sulfur colloid. Estimation of the uptake rate of the labeled colloid into the liver and other parts of the RES was performed through the use of a two-compartment model. Animals with small liver or subcutaneous tumors showed an increased activity of both the hepatic and the extrahepatic RES. Animals with large retroperitoneal tumors showed a significant decrease in the RE function of the liver. In these animals the function of the extrahepatic RES was not changed compared to controls but was, however, significantly decreased compared to animals with smaller tumors. The findings may reflect a difference in the impact of tumor size on RE function extra- and intrahepatically.

Plasma levels of a lysosomal enzyme, beta-hexosaminidase (beta-N-acetylglucosaminidase, EC 3.2.1.30) were studied in Wistar rats after administration of 99mTc -sulfur colloid, 198Au colloid, gelatine (Haemaccel), alcohol, methylpalmitate and zymosan. The activity of beta-hexosaminidase was increased 10, 30 and 60 min after the zymosan injection. After 24 and 48 h, enzyme levels had returned to those at outset. The transient release of beta-hexosaminidase probably occurred only during the phagocytosis of zymosan which was evaluated by histological examination of lung, liver and spleen. After the injection of all other agents tested, no significant aberration of beta-hexosaminidase levels was seen. Activity distribution of the radio-labeled colloids revealed differences in organ uptake which were attributed to a difference in colloid particle size. Although the colloids tested have been used extensively for determination of reticuloendothelial function and histological studies suggest phagocytosis of the particles, their administration did not affect plasma beta-hexosaminidase levels. Since lysosomal enzymes are cleared from the blood predominantly by liver macrophages, the primary location of particle phagocytosis may explain the present findings.

Reticuloendothelial (RE) function was evaluated by measuring the biokinetics of a standardized 99Tcm-sulphur colloid. Methyl palmitate was administered intravenously on two consecutive days. A statistically significant reduction in the colloid uptake rate of the liver was registered after methyl palmitate administration. Histological examination revealed no signs of destruction of RE cells or microembolization. Inoculation of an experimental nitrosoguanidine-induced transplantable adenocarcinoma to the liver was performed in 16 rats one day after methyl palmitate administration and in 16 controls. Tumor size was significantly larger in methyl-palmitate-treated animals at 7 and 14 days after inoculation. Survival was significantly decreased in methyl-palmitate-treated rats. These rats showed signs of fatty vacuolization and necrosis of liver parenchyma earlier than controls. Analyses of beta-hexosaminidase and lactate dehydrogenase revealed no deviation of enzyme levels either before or after tumor inoculation. The results indicate that a temporary suppression of RE function at the time of tumor inoculation may influence subsequent tumor growth.

Reticulo-endothelial function was evaluated by measuring the biokinetics of a standardized 99mTc-sulphur colloid using scintillation camera technique in rats with biliary obstruction. There was no difference in the uptake of the colloid in the liver (K1) between sham operation and biliary obstruction at 1 week and 3 weeks. However, when corrected for changes in liver volume, the corrected colloidal uptake rate (cK1) of the liver was significantly decreased in 1 week's biliary obstruction (P less than 0.005 compared with sham operation) and 3 weeks' biliary obstruction (P less than 0.025 compared with 1 week obstruction). Colloidal uptake rate of the extrahepatic reticulo-endothelial system (K2) was significantly increased (P less than 0.005) in rats with 3 weeks' biliary obstruction. Activity distribution of 99mTc-sulphur colloid in 3 weeks' biliary obstruction was significantly decreased in both total organ basis and per gram basis (P less than 0.005). The results demonstrated a depression of RE activity of the liver in biliary obstruction.

Studies of the activity uptake of radiolabelled 99mTc2S7 colloid in different tissues showed a moderately increased uptake in the lung 1 week and a greatly increased uptake 3 weeks after permanent bile duct occlusion. Three weeks after bile duct occlusion the activity uptake was also slightly increased in the spleen and moderately reduced in the liver. In pulmonary tissue of cholestatic rats, the levels of alkaline and acid phosphatase, beta-glucuronidase, and beta-hexosaminidase were determined after 6 weeks. The pulmonary contents of beta-glucuronidase was increased tenfold, and that of beta-hexosaminidase was increased fourfold in cholestasis. Histochemical investigation showed that the lysosomal enzymes were located in the macrophages, which in cholestasis were abundant in alveolar walls and inside alveoli. Macrophages were also frequently seen to engorge pulmonary veins.

Hepatic reticuloendothelial function was measured in 6 experimental groups of rats with various portasystemic shunts or total liver arterialization by computer calculation of the hepatic uptake rate of intravenously injected 99mTc-sulphur colloid. Marked reduction of the hepatic reticuloendothelial system (RES) function was found both 1 and 3 weeks after the construction of a mesentericocaval or conventional end-to-side portacaval shunt. Hepatic RES function was also lowered both 1 and 3 weeks after a modified portacaval shunt, but the reduction was much less pronounced. Total liver arterialization produced a similar mild reduction of hepatic RES function after 1 week; however, there was no longer any significant reduction after 3 weeks. This study concludes that total liver arterialization ameliorates the negative effect that portasystemic shunting has on hepatic RES function.

The [99mTc]sulfur colloid distribution in rat organs was investigated after the administration of different amounts of colloid particles. Saturation of the liver and spleen was not observed. Blood clearance was significantly reduced 15 min after injection above approximately 3 X 10(9) particles per kg body weight. With an increasing number of injected particles, lung uptake increased and bone marrow uptake decreased. Microfiltration studies showed that the colloid is unaffected by dilution with saline but may be affected after incubation in normal rat plasma. We conclude that the distribution of [99Tc]sulfur colloid in organs varies with the number of injected particles and therefore, is not dependent upon the blood flow to the reticuloendothelial organs alone. The "critical colloid dose" may differ among the reticuloendothelial organs and cannot, therefore, be evaluated by blood clearance measurements alone. The considerable influence of the number of injected colloid particles on bone marrow uptake should also be recognized when carrying out dosimetric calculations.