Technetium-99m labelled LDL as a tracer for quantitative LDL scintigraphy. II. 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 (99mTc-LDL) reflects the hepatic LDL receptor activity and to what extent the non-LDL receptor-dependent 99mTc-LDL uptake by non-parenchymal cells relates to the diagnostic utility of quantitative 99mTc-LDL scintigraphy of the liver. New Zealand White rabbits and Watanabe Heritable Hyperlipidaemic rabbits, which were sacrificed 24 h after simultaneous injection of 99mTc-LDL and iodine-125 labelled LDL, were clearly discriminated by their hepatic 99mTc-LDL uptake according to their genetically different hepatic LDL receptor activity. Yet the hepatic 99mTc-LDL uptake exceeded the 125I-LDL uptake in all animals. The different hepatic uptake of the tracers was elucidated in the isolated perfused rat liver and was due to rapid intracellular degradation and the release of low molecular catabolites of 125I-LDL. In contrast, 99mTc activity was trapped in the liver. Analysis of biliary 99mTc activity provided evidence for the excretion of 99mTc-labelled apolipoprotein B. The amount of biliary excreted protein-bound 99mTc was linked to total hepatic 99mTc-LDL uptake and presumably reflected LDL receptor-mediated apolipoprotein excretion. Collagenase liver perfusion in Sprague-Dawley rats 90 min following simultaneous injection of 99mTc- and 125I-LDL and subsequent cell separation by gradient centrifugation revealed that 99mTc-LDL and 125I-LDL had a comparably low uptake into non-parenchymal cells; thus its contribution can be neglected for scintigraphic purposes. Planar scintigraphy was performed in New Zealand White and Watanabe Heritable Hyperlipidaemic rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)
Leitha
T
T
University Clinic of Nuclear Medicine, University of Vienna, Austria.
Staudenherz
A
A
Gmeiner
B
B
Hermann
M
M
Hüttinger
M
M
Dudczak
R
R
D000818:Animals; D005260:Female; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL / Q000493:pharmacokinetics; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism*; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D011817:Rabbits; D011877:Radionuclide Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley; D011973:Receptors, LDL / Q000378:metabolism*
D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; D015609:Organotechnetium Compounds; D011973:Receptors, LDL; C058312:technetium Tc 99m low-density lipoprotein