Incorporation of an I-125-labeled hexa-iodinated diglyceride analog into low-density lipoprotein and high specific uptake by cells of cervical carcinoma cell lines

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 nu mber of cancer cell lines were found to have higher LDL receptor activity t han normal cells. Such differential uptake between tumor and normal cells m ay provide a unique opportunity to use LDL as a tumor-specific carrier of r adiopharmaceuticals for the clinical management of cancer. In this study, a n I-125-labeled hexa-iodinated diglyceride analog, 1,3-dihydroxypropan-2-on e 1,3-diiopanoate (DPIP), was synthesized and incorporated into LDL using a fusion technique. It was found that approximately 500 [I-125] DPIP molecul es 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 u ptake of the [I-125]DPIP-LDL conjugate, It was shown that the [I-125]DPIPLD L conjugate was specifically bound to and taken up by cervical tumor cells through an LDL receptor-mediated endocytosis pathway. The results suggest t hat LDL may be a selective carrier for delivering hydrophobic radiopharmace uticals to cancer cells and particularly for the diagnosis of cervical tumo rs. (C) 1999 by Radiation Research Society.