title: Incorporation of an (125)I-labeled hexa-iodinated diglyceride analog into low-density lipoprotein and high specific uptake by cells of cervical carcinoma cell lines.
abstract: The feasibility of using low-density lipoprotein (LDL) to deliver cytotoxic drugs to tumor cells has been explored since the 1980s, when cells of a number of cancer cell lines were found to have higher LDL receptor activity than normal cells. Such differential uptake between tumor and normal cells may provide a unique opportunity to use LDL as a tumor-specific carrier of radiopharmaceuticals for the clinical management of cancer. In this study, an (125)I-labeled hexa-iodinated diglyceride analog, 1, 3-dihydroxypropan-2-one 1,3-diiopanoate (DPIP), was synthesized and incorporated into LDL using a fusion technique. It was found that approximately 500 [(125)I] DPIP molecules were incorporated into each LDL particle. Cells of three human cervical tumor cell lines, HeLa, SiHa and C-33A, were used to examine the cellular uptake of the [(125)I]DPIP-LDL conjugate. It was shown that the [(125)I]DPIP-LDL conjugate was specifically bound to and taken up by cervical tumor cells through an LDL receptor-mediated endocytosis pathway. The results suggest that LDL may be a selective carrier for delivering hydrophobic radiopharmaceuticals to cancer cells and particularly for the diagnosis of cervical tumors.
authors.affiliation: School of Pharmacy, Faculty of Medicine, Memorial University of Newfoundland, 300 Prince Philip Drive, St. John's, Newfoundland, A1B 3V6, Canada.
authors.forename: W
authors.initials: W
authors.lastname: Xiao
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: J M
authors.initials: JM
authors.lastname: Ryan
authors.forename: A
authors.initials: A
authors.lastname: Pater
authors.forename: H
authors.initials: H
authors.lastname: Liu
mesh_terms: D001665:Binding Sites; D002277:Carcinoma / Q000000981:diagnostic imaging / Q000378:metabolism*; D004337:Drug Carriers; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007457:Iodine Radioisotopes; D007480:Iopanoic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000493:pharmacokinetics; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*
chemical_list: C121277:1,3-dihydroxypropan-2-one 1,3-diiopanoate; D004337:Drug Carriers; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; D019275:Radiopharmaceuticals; D007480:Iopanoic Acid