TY - JOUR
T1 - Imaging of hepatic low density lipoprotein receptors by radionuclide scintiscanning in vivo
AU - Huettinger, M.
AU - Corbett, J. R.
AU - Schneider, W. J.
AU - Willerson, J. T.
AU - Brown, M. S.
AU - Goldstein, J. L.
PY - 1984
Y1 - 1984
N2 - The low density lipoprotein (LDL) receptor mediates the cellular uptake of plasma lipoproteins that are derived from very low density lipoproteins (VLDL). Most of the functional LDL receptors in the body are located in the liver. Here, we describe a radionuclide scintiscanning technique that permits the measurement of LDL receptors in the livers of intact rabbits. 123I-labeled VLDL were administered intravenously, and scintigraphic images of the liver and heart were obtained at intervals thereafter. In seven normal rabbits, radioactivity in the liver increased prgressively between 1 and 20 min after injection, while radioactivity in the heart (reflecting that in plasma) decreased concomitantly. In Watanabe-heritable hyperlipidemic rabbits, which lack LDL receptors on a genetic basis, there was little uptake of 123I-labeled VLDL into the liver and little decrease in cardiac radioactivity during this interval. These findings demonstrate that the LDL receptor is necessary for the hepatic uptake of VLDL-derived lipoproteins in the rabbit. Two conditions that diminish hepatic LDL receptor activity, cholesterol-feeding and prolonged fasting, also reduced the uptake of 123I-labeled VLDL in the liver as measured by scintiscanning. The data suggest that radionuclide scintiscanning can be used as a noninvasive method to quantify the number of LDL receptors expressed in the liver in vivo.
AB - The low density lipoprotein (LDL) receptor mediates the cellular uptake of plasma lipoproteins that are derived from very low density lipoproteins (VLDL). Most of the functional LDL receptors in the body are located in the liver. Here, we describe a radionuclide scintiscanning technique that permits the measurement of LDL receptors in the livers of intact rabbits. 123I-labeled VLDL were administered intravenously, and scintigraphic images of the liver and heart were obtained at intervals thereafter. In seven normal rabbits, radioactivity in the liver increased prgressively between 1 and 20 min after injection, while radioactivity in the heart (reflecting that in plasma) decreased concomitantly. In Watanabe-heritable hyperlipidemic rabbits, which lack LDL receptors on a genetic basis, there was little uptake of 123I-labeled VLDL into the liver and little decrease in cardiac radioactivity during this interval. These findings demonstrate that the LDL receptor is necessary for the hepatic uptake of VLDL-derived lipoproteins in the rabbit. Two conditions that diminish hepatic LDL receptor activity, cholesterol-feeding and prolonged fasting, also reduced the uptake of 123I-labeled VLDL in the liver as measured by scintiscanning. The data suggest that radionuclide scintiscanning can be used as a noninvasive method to quantify the number of LDL receptors expressed in the liver in vivo.
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U2 - 10.1073/pnas.81.23.7599
DO - 10.1073/pnas.81.23.7599
M3 - Article
C2 - 6594702
AN - SCOPUS:0021745305
SN - 0027-8424
VL - 81
SP - 7599
EP - 7603
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 23 I
ER -