Abstract 1853: Lipiodol-based emulsion to disrupt oxygenation and lipid homeostasis of liver tumors
Authors: Pillai Smitha R. , Phadatare Pravin , Ortiz Antonio , Barakat Elie , El-Haddad Ghassan 
Published: September 2020

Abstract
Trans-arterial embolic therapies for liver tumors are used routinely in patients with hepatocellular carcinoma (HCC) and patients with liver dominant metastatic disease. Lipiodol® (Ethiodized oil; ethyl esters of iodized fatty acids of poppy seed oil) has been historically used as a vehicle for delivering chemotherapeutic agents as part of chemoembolization (cTACE) of liver tumors. Lipiodol's role in cTACE is to visualize the delivery of the mixture under fluoroscopy, emulsification and delivery of the chemotherapeutic agent, and as a microembolic agent itself. Contrary to previous studies that showed better outcome in patients with HCC treated with cTACE compared to bland embolization (TAE), more recent studies demonstrated no significant difference between drug-eluting chemoembolization and bland embolization (TAE), negating the added benefit of chemotherapy as a required agent when performing liver embolization of HCC. Therefore, we hypothesized that the added benefit of cTACE over TAE stems from the Lipiodol-based emulsion and not chemotherapy. We performed embolization of liver tumors using Lipiodol-Isovue emulsion and bland particles (TALE) but replacing chemotherapy with Isovue-300® (Iopamidol, a non-ionic iodinated contrast agent). Our preliminary data of 5 patients with non-resectable HCC (1 to 14.9 cm) treated with TALE without systemic therapy were followed for at least 5 months and response was evaluated using RECIST and mRECIST. By mRECIST, 3 patients had complete response (CR), one had a partial response (PR) and one could not be evaluated since the biopsy-proven HCC was hypovascular. Using RECIST 1.1 criteria, two patients had a stable disease (SD), and 3 had PR, including Interestingly CR of one of 2 tumors. We also treated 5 patients with metastatic renal cell carcinoma (RCC) using TALE with tumors ranging from 2.2 to 4.3 cm; using RECIST, three patients had PR, one SD, and one PD (progressive disease). Based on these results, we investigated the cytotoxic effects of Lipiodol in HCC and RCC cell lines Huh7 and A498. Lipiodol-Isovue emulsions were cytotoxic to these cells while viability of a normal/primary cell line HEK293 was not affected. Additionally, Lipiodol alone showed similar cytotoxic effects as the emulsions. Furthermore, Lipiodol was taken up by cells as seen by staining with Nile Red, a fluorescent dye that stains neutral lipids in lipid droplets using confocal microscopy. Our in vitro data indicate that RCC and HCC cells are more vulnerable to Lipiodol-induced lipotoxicity than non-cancerous primary kidney epithelial cells. There might be a synergistic effect between causing hypoxia as a result of blocking blood flow to the tumors during liver embolization and disrupting lipid homeostasis with the use of a Lipid-based emulsion. Our studies unravel a potential metabolic vulnerability that can be exploited therapeutically with liver-directed therapies.
Citation Format: Smitha R. Pillai, Pravin Phadatare, Antonio Ortiz, Elie Barakat, Ghassan El-Haddad. Lipiodol-based emulsion to disrupt oxygenation and lipid homeostasis of liver tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1853.