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Radiotracers for Low Density Lipoprotein Biodistribution Studies In Vivo: Technetium-99m Low Density Lipoprotein Versus Radioiodinated Low Density Lipoprotein Preparations

Mount Sinai School of Medicine, New York
College of Physicians and Surgeons, Columbia University, New York, New York

Correspondence: For reprints contact: Shankar Vallabhajosula, PhD, Andre Meyer Department of Physics-Nuclear Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, New York.

ABSTRACT

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.

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