Metabolic imaging with gallium-68- and indium-111-labeled low-density lipoprotein

Low-density lipoprotein (LDL) labeled with either gallium-68 (68Ga) or indium-111 (111In) was evaluated as a potential PET or SPECT radiopharmaceutical for determination of hepatic lipoprotein metabolism in rabbits. Gallium-68 or 111In was linked to LDL via diethylenetriaminepentaacetic acid (DTPA) with a 25-70% radiochemical yield. Studies in vivo that compared 68Ga- or 111In-DTPA-LDL with dilactitol-[125I]-tyramine LDL and 131I-LDL showed that both 68Ga- and 111In-labeled LDL behaved as residualizing radiotracers. Localization of radioactivity within the liver of normal rabbits was visualized clearly with [68Ga]DTPA-LDL by PET and with [111In]DTPA-LDL by gamma scintigraphy. Significant differences were observed in hepatic uptake of normal compared with hypercholesterolemic rabbits in which low-capacity LDL receptor-mediated catabolism was saturated. Gallium-68 and 111In-DTPA-LDL are attractive radiopharmaceuticals for noninvasive delineation of tissue LDL metabolism under normal and pathophysiologic conditions.