Mechanism of hepatic extraction of gelatinized 99mTechnetium sulfur colloid

Abstract

Hepatic extraction, cellular and subcellular localization of gelatin stabilized Tc-99m sulfur colloid was studied in the rat model with time sequenced microautoradiography from 15 min to 24 h following I.V. administration of the tracer. Hepatic lobular and cellular distribution, quality and quantity of focal grain pattern, grain clusters, remained essentially constant for the period of study. Grain clusters were associated predominantly with Kupffer cells lining the peripheral segment of hepatic lobular sinusoids. Subcellular localization of gelatinized Tc sulfur colloid, stained prior to the I.V. administration with osmium tetroxide, was demonstrated with a transmission electron microscope in unosmicated liver tissue. Extracted Tc sulfur colloid particles were attached in groups to cytoplasmatic membranous intrasinusoidal projections of activated Kupffer cells. Intracytoplasmatic phagocytosis was not demonstrated. The kinetic arrest and en groupe extraction of Tc sulfur colloid particles at the Kupffer cell membrane suggests a specific membrane receptor site and specific Tc sulfur colloid particle-plasma protein interaction at the time of extraction. Hepatic extraction of gelatinized Tc sulfur colloid thus reflects primarily extra and intra hepatic hemodynamics and does not serve as an indicator of phagocytic hepatic reticuloendothelial system function.

Release of ß-Hexosaminidase after Administration of Different Agents Affecting the Reticuloendothelial System

“…Similar results have been obtained concerning the 99mTc-sulfur colloid. These histological findings were also confirmed by ultrastructural stud ies [31], However, autoradiographic studies by others have failed to demonstrate radioac tive material intracellularly [9], Ultrastruc tural studies of the uptake of sulfur colloid by hepatic macrophages demonstrated the parti cles in clusters on the surface of Kupffer cells but not intracellularly [16], These differences may be explained by different colloid prepa rations, since differences in colloid particle size may influence the organ uptake [3,40].…”

“…In the present study, none of the injected colloids caused significant al terations in plasma levels of ß-hexosaminidase. This may be explained by the fact that most particles, during the time of study (60 min), merely adhere to the surface of phagocytes [16]. Another possible explana tion is that the released enzyme is imme diately cleared from the blood by neighbor ing Kupfifer cells and never reach the sys temic circulation, in contrast to enzyme re leased from other organs such as the lungs [37,42], Alcohol depresses phagocytic activity as measured by the clearance of microaggregated albumin [2], Acute and chronic admin istration of alcohol has been associated with delayed endotoxin clearance in rats which was related to the dose of alcohol [26].…”

“…198Au colloid has also been used as an agent for studies of the RES [9,40]. In a comparative study of the localiza tion of injected 99mTc-sulfur colloid and 198Au colloid, only the 198Au colloid was retrieved intracellularly in Kupffer cells [9], George et al [ 16] also failed to show ingestion of 99mTc-sulfur colloidal particles in Kupffer cells. However, histological and ultrastruc tural studies in our laboratory have shown phagocytosis of the 99mTc-sulfur colloid [31], The stimulatory effect on the RES of zymo san has been explored by numerous investi gators [12,13,29,30,41,46], Histological examinations have revealed that zymosan is phagocytized by macrophages [19,41],…”

“…These methods are based upon studies of the fate of injected colloidal parti cle uptake by macrophages [9,16]. In earlier studies of RE function, we have used a highly standardized preparation of 99mTc-sulfur col loid [28,31,32].…”

Factors Affecting the Quantitative Liver?Spleen Scan in Normal Individuals

“…Thus, the quantitative (QLSS) using single-photon emission computerized tomography (SPECT) can precisely measure sulfur colloid distribution (1)(2)(3)(4)(5)(6)(7)(8) and organ volumes (9). This technique for measuring sulfur colloid distribution is based on phagocytic activity of the reticuloendothelial (RE) cells that extract colloid particles and thus reflects hepatic blood flow and hepatic mass (1,5,7,(10)(11)(12)(13)(14)(15)(16). We have demonstrated that the perfused hepatic mass (PHM) index of sulfur colloid distribution represents the functional (nonfibrotic) mass of the liver (4) correlating Digestive Diseases and Sciences, Vol.…”