BIODISTRIBUTION STUDY OF TC-99M-LABELED LDL IN B16-MELANOMA-BEARING MICE - VISUALIZATION OF A PREFERENTIAL UPTAKE BY THE TUMOR

Since there is strong evidence of a preferential LDL accumulation in t umor cells, LDL might be of interest for tumor imaging. We have tested the ability of Tc-99m-LDL in tumor imaging with B 16-melanoma-bearing mice as a model for further applications in human studies. The LDL fi xation rate was higher with Tc-99m-labeled LDL than with I-125 labeled LDL. Since technetium-99m remains trapped in the cells, Tc-99m-LDL is a well-adapted radioligand because of information given by this radio tracer on the receptor metabolism. We observed that, at early growth s tages, the tumor took up the LDL at a maximal rate, suggesting differe nces in cholesterol metabolism as a function of tumor growth. Accumula tion of label in the tumor area was perfectly observable in tumor-bear ing mice on scintigraphic images. Computerized quantification of the r egions of interest (as well as biodistribution studies including killi ng of the animals) showed a 1.81-fold increase in uptake by the tumor as compared to the liver and a 28-fold increase as compared with corre sponding normal tissue (muscle of the left leg) at day 8 of tumor grow th. These data give strong support to the value of this non-invasive m ethod in visualizing and quantifying the tissue LDL uptake in vivo, in cluding the precise information provided by nuclear scintigraphy on th e distribution of the radiolabeled LDL in the different tissues. Tc-99 m-LDL could be an efficient tool for further diagnostic or therapeutic exploration in cancer patients.