Abstract B33: Multifunctional formulation for dual imaging and magnetic hyperthermia therapy of liver cancer: A preclinical feasibility study

Abstract

Purpose: Magnetic hyperthermia with local delivery of iron oxide nanoparticles (NP) offers a promising therapeutic alternative for primary liver cancer. Our aim was to explore the therapeutic potential of local NP injection, using a nanoparticle- ethiodized oil (lipiodol) emulsion (NLE), in xenograft HepG2 mouse models of liver cancer and in orthotopic VX2 rabbit liver cancer models. Materials/Methods: NLE comprises lipiodol (50% w/v), polysorbate 20 (Tween 20, 0.2% w/v) and biocompatible Fe3O4 nanoparticles (BNF, 49.8% w/v). In vivo mice experiments included intra-tumor injections of a) NLE (n=20), b) BNF (n=12), c) PBS (n=14) in Foxnu1 mice bearing flank xenograft HepG2 tumors with and without AMF hyperthermia exposure (15-min, 300-700 Gauss, 150 kHz, 18 hours post-injection, with core and peri-tumor temperature measurements). Mice were either euthanized at 1-7 days or observed for tumor growth delay. Rabbit experiments included intra-arterial injections of NLE (n=8) with (n=4) and without (n=4) subsequent AMF hyperthermia exposure (20 min, 300 Gauss, 150 KHz, 48 hours (n=2) or 7 days (n=2) post-injection, with core and peri-tumor temperature measurements). Rabbits were euthanized at 3 or 7 days. Rabbits were imaged at baseline and before euthanasia in a clinical 320-slice CT scanner, as well as in a clinical 3T MR scanner. Imaging analysis included CT perfusion measurements, MR T2* measurements and co-registration of lipiodol and iron content. Pathologic analysis for all studies included evaluation of tumor necrosis, lipiodol and iron distribution.. Results: In mice, average maximum tumor temperature increase was 7.4±0.5°C for NLE (n=8) and 5.4±0.3°C for NP (n=5). At 24 days, there was a 4-fold difference in tumor growth delay between PBS and NLE-AMF heated tumors. Increased tumor necrosis was observed at 7 days in the NLE group. Intra-tumor iron distribution of NLE samples showed a characteristic distribution of NLE along the vascular tumor pathways at the tumor rim. In rabbits, average maximum tumor temperature increase was 3.2±0.5°C. Similarly, increased tumor necrosis was observed at 7 days and intra-tumor iron was seen deposited at the tumor rim. While CT imaging revealed primarily lipiodol deposition, MR imaging was very sensitive in detecting iron distribution, even in non-targeted areas. Conclusion: Preliminary in vivo data of the proposed NLE formulation for magnetic hyperthermia and dual imaging show potential for intra-tumor delivery and therapy in HepG2 xenograft mice models and intra-arterial delivery and therapy in the VX2 liver cancer model, with MRI/CT capabilities. Histological analysis of NLE treated tumors confirmed intra-tumour iron deposition with increased cellular damage. Initial results are encouraging and motivate further development for clinical translation. Citation Format: Eleni Liapi, Sahar Mirpour, Madhav Seshadri, Anilchandra Attaluri, Michele Wabler, Haoming Zhou, Robert Ivkov. Multifunctional formulation for dual imaging and magnetic hyperthermia therapy of liver cancer: A preclinical feasibility study. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr B33.