TC-99M LABELED LDL AS A TRACER FOR QUANTITATIVE LDL SCINTIGRAPHY .2. IN-VIVO VALIDATION, LDL RECEPTOR-DEPENDENT AND UNSPECIFIC HEPATIC-UPTAKE AND SCINTIGRAPHIC RESULTS

The purpose of this study was to determine whether the hepatic uptake of dialysed technetium-99m labelled low-density lipoprotein (Tc-99m-LD L) reflects the hepatic LDL receptor activity and to what extent the n on-LDL receptor-dependent Tc-99m-LDL uptake by non-parenchymal cells r elates to the diagnostic utility of quantitative Tc-99m-LDL scintigrap hy of the liver. New Zealand White rabbits and Watanabe Heritable Hype rlipidaemic rabbits, which were sacrificed 24 h after simultaneous inj ection of Tc-99m-LDL and iodine-125 labelled LDL, were clearly discrim inated by their hepatic Tc-99m-LDL uptake according to their genetical ly different hepatic LDL receptor activity. Yet the hepatic Tc-99m-LDL uptake exceeded the I-125-LDL uptake in all animals. The different he patic uptake of the tracers was elucidated in the isolated perfused ra t liver and was due to rapid intracellular degradation and the release of low molecular catabolites of I-125-LDL. In contrast, Tc-99m activi ty was trapped in the liver. Analysis of biliary Tc-99m activity provi ded evidence for the excretion of Tc-99m-labelled apolipoprotein B. Th e amount of biliary excreted protein-bound Tc-99m was linked to total hepatic Tc-99m-LDL uptake and presumably reflected LDL receptor-mediat ed apolipoprotein excretion. Collagenase liver perfusion in Sprague-Da wley rats 90 min following simultaneous injection of Tc-99m and I-125- LDL and subsequent cell separation by gradient centrifugation revealed that Tc-99m-LDL and I-125-LDL had a comparably low uptake into non-pa renchymal cells; thus its contribution can be neglected for scintigrap hic purposes. Planar scintigraphy was performed in New Zealand White a nd Watanabe Heritable Hyperlipidaemic rabbits. The different hepatic L DL receptor activities of the two groups were reflected by the slope o f the liver/heart ratios over 24 h post injection and correlated well with their respective cumulative hepatic Tc-99m-LDL uptake. Thus, we h ave been able to show that Tc-99m-LDL scintigraphy. using dialysed Tc- 99m-LDL can quantitate different genetically determined hepatic LDL re ceptor activities. The finding of the biliary excretion of Tc-99m-labe lled apolipoprotein B deserves further attention for its possible diag nostic utility.