RADIOTRACERS FOR LOW-DENSITY LIPOPROTEIN BIODISTRIBUTION STUDIES INVIVO - TECHNETIUM-99M LOW-DENSITY LIPOPROTEIN VERSUS RADIOIODINATED LOW-DENSITY LIPOPROTEIN PREPARATIONS

In an attempt to characterize the in vivo behavior of [99mTc] low density lipoprotein (LDL), biodistribution studies were performed in normal and hypercholesterolemic (HC) rabbits. In normal rabbits, 24 hr after the injection of [99mTc]LDL, 99mTc activity accumulated mainly in adrenal glands, spleen, liver, and kidney. In HC rabbits, however, there was a marked reduction of 99mTc activity in these organs. In both normal and HC rabbits, < 17% of 99mTc activity appeared in the 24-hr urine following injection of [99mTc]LDL, suggesting that in vivo, [99mTc]LDL is trapped and accumulated within the tissues. Direct comparison of [99mTc]LDL, 125I-native-LDL and [131I]tyramine cellobiose-LDL (the previously validated trapped radioligand) in normal rabbits, demonstrated that the biodistribution of [99mTc]LDL was similar to that of [131I]tyramine cellobiose-LDL. The adrenal glands, liver, and spleen accumulated significantly greater quantities of 99mTc and 131I activity per gram of tissue than 125I (from native-LDL). In addition, imaging studies in monkeys, showed that the hepatic uptake and retention of [99mTc] LDL was similar to that of [131I]tyramine cellobiose LDL. In contrast, radioiodine from native-LDL was deiodinated in liver with subsequent excretion into the intestine. These results suggest that [99mTc]LDL acts as a trapped ligand in vivo and should therefore, be a good tracer for noninvasive quantitative biodistribution studies of LDL.