1. The intrasplenic kinetics of granulocytes, isolated in plasma and labelled in plasma with 111 In-tropolonate, have been studied in normal subjects, patients with negative studies for inflammatory disease and patients with positive studies, with the aim of identifying the nature of splenic activity seen after 111 In-labelled granulocyte administration. 2. Up to 40 min after injection, 111 In activity was visible only in major blood vessels, liver and spleen, with slight, abnormal activity visible in most of those with positive scans. The time courses of uptake of hepatic and splenic activity were different, with liver activity rapidly reaching a plateau and splenic activity increasing mono-exponentially to a plateau achieved between 20 and 40 min. 3. The clear difference between the shapes of the hepatic and splenic uptake curves and the magnitude of the splenic uptake rate constant indicated that splenic activity represented reversible uptake. 4. The application of deconvolution analysis to the blood and splenic time-activity curves generated a splenic retention (or washout) curve consistent with dynamic exchange of granulocytes between blood and spleen. The slope of this curve indicated an intrasplenic granulocyte transit time of 9.3 (± se 0.6) min. 5. Taking splenic activity to be reversible, comparison of the 111 In signal from the spleen 40 min after injection of 111 In-labelled granulocytes with that given from the spleen after the injection of 111 In-labelled erythrocytes (relative to their respective blood levels) indicated that intrasplenic granulocyte transit time was 14.4 (± se 1.1) times that of erythrocytes. Based on actual erythrocyte time, this corresponds to a granulocyte transit time of 8.6-11.5 min, in close agreement with the estimate based on deconvolution analysis. 6. The reversibility of splenic 111 In activity after labelled granulocyte injection was confirmed by observing falls in splenic activity between 40 min and 24 h and between 3 and 24 h, which were greater in patients with inflammatory disease than those without. Furthermore, a significant correlation was recorded between this fall and the fraction of the dose of 111 In excreted in the faeces in patients with inflammatory bowel disease (IBD). 7. We conclude that the normal spleen contains a reservoir of granulocytes which is in dynamic equilibrium with circulating granulocytes (CGP). This pool therefore is a major component of the body's marginating granulocyte pool (MGP). The mean transit time of granulocytes through the spleen, about 10 min, is remarkably similar to that of platelets.

1. The rate of clearance from blood of 111 In-labelled heat damaged autologous erythrocytes (HD-RBC) has been compared with that of simultaneously injected autologous 99m Tc-labelled erythrocytes (IgG-RBC) coated with a Rhesus anti-D antibody. In 17 studies, the number of antibody molecules coating the erythrocytes was 9000 (high coating) and in nine studies the number was 5000 (low coating). 2. On gamma camera imaging, IgG-RBC uptake, at both levels of coating, could be visualized only in the spleen. HD-RBC were predominantly taken up by the spleen, although slight 111 In activity was visible in the liver. 3. The blood clearance of IgG-RBC was mono-exponential, whereas that of HD-RBC was bi-exponential. The reciprocal of the t 1/2 (the time taken for the 3 min value to fall by 50%) of the HD-RBC clearance correlated rather poorly with the rate constant of the simultaneous IgG-RBC clearance ( r = 0.47, P > 0.05 at high coating; r = 0.75, P < 0.05 at low coating). The rate constant of the second exponential of the HD-RBC clearance showed a correlation with the rate constant of IgG-RBC clearance that was closer than the reciprocal of the t 1/2 of HD-RBC clearance ( r = 0.89, P < 0.001 at high coating; r = 0.76, P < 0.05 at low coating) but significantly closer only at high coating. 4. Splenic blood flow, measured using indium labelled platelets in ten subjects, correlated closely with the initial slope of HD-RBC clearance ( r = 0.93, P <0.001). 5. By using splenic blood flow based either on platelets or on the initial slope of the HD-RBC clearance, an estimate was made of splenic IgG-RBC extraction ratio. The normal extraction ratio at high coating was about 50% and at low coating about 30%. Some patients with systemic lupus erythematosus and rheumatoid arthritis appeared to have abnormally low extraction ratios. 6. It was concluded that HD-RBC and IgG-RBC are not interchangeable as markers of splenic reticuloendothelial function; HD-RBC clearance is mainly dependent on splenic blood flow whereas IgG-RBC clearance is dependent both on splenic blood flow and splenic macrophage function. The simultaneous use of the two markers allows therefore an estimate of the splenic IgG-RBC extraction ratio, which potentially is a more specific index of splenic reticuloendothelial function than the clearance rate of either marker used alone.

1. Liposomes containing 111 In-labelled bleomycin were injected intravenously into two patients. One patient had a hepatoma and the other had secondary adenocarcinomatous deposits in the liver. 2. The tissue distribution of 111 In was determined by whole-body scanning and by measurement of the radioactivity in organs at autopsy. 3. Scans in vivo and post-mortem measurement of radioactivity indicated that liposomes accumulate predominantly in the liver, but that there is no selective uptake of liposomes by the malignant tissue. 4. The subcellular distribution of radioactivity in the liver was measured 90 min after injection by fractionation of percutaneous liver biopsies on sucrose density gradients. 5. Radioactivity within the liver was concentrated in lysosomes. 6. Electron microscopy of tissue obtained before the administration of liposomes revealed particles morphologically indistinguishable from liposomes in hepatoma cells and hepatocytes.