Targeted hyperthermia after selective embolization with ferromagnetic nanoparticles in a VX₂ rabbit liver tumor model

Hongliang Sun,¹ Linfeng Xu,¹ Tianyuan Fan,² Hongzhi Zhan,³ Xiaodong Wang,³ Yanfei Zhou,² Ren-jie Yang<sup>3

1</sup>Department of Interventional Therapy, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou, ²Pharmacy School of Beijing University, Beijing, ³Department of Interventional Therapy, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, People's Republic of China

Background: The purpose of this study was to observe the effect and feasibility of hyperthermia and the influence of heat on surrounding organs in a VX₂ rabbit liver model exposed to an alternating magnetic field after embolization with ferromagnetic nanoparticles.
Methods: Forty rabbits containing implanted hepatic VX₂ carcinomas were divided into four groups, each containing ten rabbits. Fourteen days after tumor transplantation, we opened the abdomen to observe the size and shape of the tumor. A transfemoral retrograde approach was then used for hepatic arterial catheterization in groups B, C, and D to perform angiography and embolization. The next day, three rabbits in group B and all rabbits in group D were exposed to an alternating magnetic field, and the temperature was recorded simultaneously in the center of the tumor, at the edge of the tumor, and in the normal liver parenchyma. On day 28, all animals was euthanized to observe changes in the implanted liver tumor and the condition of the abdomen. A pathologic examination was also done.
Results: Before surgery, there was no significant difference in tumor volume between the four groups. Three different temperature points (center of the tumor, edge of the tumor, and in the normal liver parenchyma) of group B under an alternating magnetic field were 37.2°C ± 1.1°C, 36.8°C ± 1.2°C, and 36.9°C ± 2.1°C, none of which were significantly different from pretreatment values. Three points basal temperature in group D showed no significant difference (F = 1.038, P = 0.413). Seven to 26 minutes after hyperthermia, the temperature at the center of the tumor and at the edge of the tumor in group D was significantly different from the corresponding points in group B and from normal liver tissue in group D (F_{B–D center} = 5.431, P_{B–D center} = 0.041, F_{B–D edge} = 9.744, P_{B–D edge} = 0.011; F_D = 8.379, P_D = 0.002). The highest temperature recorded at the rim of the tumor was 46°C in group D. Fourteen days later, the tumor volume in the four groups was group A 31.4 ± 20.6 cm³, group B 26.7 ± 18.2 cm³, group C 28.7 ± 9.1 cm³, and group D 25.8 ± 13.9 cm³, with no significant difference found between the groups (F = 0.218, P = 0.883). The increase in tumor volume was greatest in group A and least in group D, while that in groups B and D was similar.
Conclusion: It is feasible to treat a VX₂ tumor in an alternating magnetic field after embolization with magnetic nanoparticles without a significant effect on the surrounding normal liver parenchyma.

Keywords: hyperthermia, ferromagnetic nanoparticles, Lipiodol^®, hepatocellular carcinoma, animal model