Biodistribution study of 99mTc-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 tumor cells, LDL might be of interest for tumor imaging. We have tested the ability of 99mTc-LDL in tumor imaging with B16-melanoma-bearing mice as a model for further applications in human studies. The LDL fixation rate was higher with 99mTc-labeled LDL than with 125I labeled LDL. Since technetium-99m remains trapped in the cells, 99mTc-LDL is a well-adapted radioligand because of information given by this radiotracer on the receptor metabolism. We observed that, at early growth stages, the tumor took up the LDL at a maximal rate, suggesting differences in cholesterol metabolism as a function of tumor growth. Accumulation of label in the tumor area was perfectly observable in tumor-bearing mice on scintigraphic images. Computerized quantification of the regions of interest (as well as biodistribution studies including killing 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 corresponding normal tissue (muscle of the left leg) at day 8 of tumor growth. These data give strong support to the value of this non-invasive method in visualizing and quantifying the tissue LDL uptake in vivo, including the precise information provided by nuclear scintigraphy on the distribution of the radiolabeled LDL in the different tissues. 99mTc-LDL could be an efficient tool for further diagnostic or therapeutic exploration in cancer patients.
Ponty
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E
Laboratoire de Ciblage en Thérapeutique, UFR des Sciences Pharmaceutiques, Toulouse, France.
Favre
G
G
Benaniba
R
R
Boneu
A
A
Lucot
H
H
Carton
M
M
Soula
G
G
D000818:Animals; D002455:Cell Division / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D015902:Gamma Cameras; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL / Q000493:pharmacokinetics*; D008546:Melanoma, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D011973:Receptors, LDL / Q000378:metabolism; D013667:Technetium; D014018:Tissue Distribution
D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; D015609:Organotechnetium Compounds; D011973:Receptors, LDL; C058312:technetium Tc 99m low-density lipoprotein; D013667:Technetium