P-0075 18F-FDG Uptake in Hepatocellular Carcinoma Cell Lines: Correlation with Multidrug Resistance Proteins Expression

Abstract

IntroductionMalignant cells require high energy via glycolytic generation of ATP for cell proliferation and survival. Positron emission tomography (PET) using radiolabelled glucose analogue 18F-FDG allows detecting increased glycolytic events in tumor cells. Hepatocellular carcinoma (HCC) is highly resistant to chemotherapy, which is due in part to the overexpression of multidrug resistance proteins (MDR). It is known that 18F-FDG uptake in HCC is associated with tumor differentiation and with the expression of these proteins. This study aims to evaluate the uptake and retention of 18F-FDG into two human HCC cell lines with different expression levels of p53 and to correlate with the expression of three MDR proteins: the P-Glycoprotein (Pgp), the multidrug resistance–associated protein (MRP1) and the lung resistance-related protein (LRP). MethodsThe human HCC cell lines used were HepG2 (wp53) and Huh7 (mp53). Cell suspensions were incubated with 2x106 cells per ml with 18F-FDG (25 µCi/mL). Samples of 200 µl were collected to Eppendorf tubes at different periods of time, which were centrifuged in order to separating the supernatant from the pellet. Radioactivity of pellet and supernatant was measured in a well counter. The retention of 18F-FDG was obtained incubating cell suspension with the radiopharmaceutical for 60 minutes. Then, the cells were centrifuged and the medium replaced, the following procedure was similar to the uptake studies. The protein levels of Pgp, MRP1 and LRP were determined by flow cytometry. ResultsIt was noted that the HuH7 cell line, that express a mutant form of p53, has the higher levels of 18F-FDG uptake and retention. The HepG2 cell line has a lower uptake and retention, and a higher expression of MRP1. The levels of Pgp and LRP expression are identical for two cell lines. ConclusionAlthough these are preliminary results it can be concluded that there is an inverse relationship between the expression of MRP1 and the levels of uptake and retention of 18F-FDG. These data may be useful in clinical practice