Local hyperthermia for esophageal cancer in a rabbit tumor model: Magnetic stent hyperthermia versus magnetic fluid hyperthermia

Abstract

Magnetic-mediated hyperthermia (MMH) is a promising local thermotherapy approach for cancer treatment. The present study investigated the feasibility and effectiveness of MMH in esophageal cancer using a rabbit tumor model. The therapeutic effect of two hyperthermia approaches, magnetic stent hyperthermia (MSH), in which heat is induced by the clinical stent that is placed inside the esophagus, and magnetic fluid hyperthermia (MFH), where magnetic nanoparticles are applied as the agent, was systematically evaluated. A rabbit esophageal tumor model was established by injecting VX2 carcinoma cells into the esophageal submucosa. The esophageal stent was deployed perorally into the tumor segment of the esophagus. For the MFH, magnetic nanoparticles (MNPs) were administered to the rabbits by intratumoral injection. The rabbits were exposed under a benchtop applicator using an alternative magnetic field (AMF) with 300 kHz frequency for the hyperthermia treatment. The results demonstrated that esophageal stents and MNPs had ideal inductive heating properties upon exposure under an AMF of 300 kHz. MSH, using a thermal dose of 46°C with a 10-min treatment time, demonstrated antitumor effects on the rabbit esophageal cancer. However, the rabbit esophageal wall is not heat-resistant. Therefore, a higher temperature or longer treatment time may lead to necrosis of the rabbit esophagus. MFH has a significant antitumor effect by confining the heat within the tumor site without damaging the adjacent normal tissues. The present study indicates that the two hyperthermia procedures have therapeutic effects on esophageal cancer, and that MFH may be more specific than MSH in terms of temperature control during the treatment.

Keywords: alternative magnetic field; esophageal cancer; esophageal stent; magnetic mediated hyperthermia; magnetic nanoparticles.

Figure 1

The two types of esophageal stents that were used in the present study.

Figure 2

Transmission electron microscopy images of MNPs. (A) Uncoated MNPs. (B) APTES-coated MNPs. MNP, magnetic nanoparticles; APTES, 3-aminopropyltriethoxysilane.

Figure 3

Experimental apparatus of the magnetic hyperthermia system (MHS).

Figure 4

Inductive heating properties of the esophageal stent under an AMF (A) Effect of stent quality with field intensity of 28.6Gs. (B) Effect of field intensity (type B stent). (C) Effect of orientation (type B stent with field intensity of 28.6Gs). Stent quality, field intensity and orientation of stent placement have effect on the inductive heating property of the stents under AMF exposure. AMF, alternative magnetic field.

Figure 5

Inductive heating properties of MNPs under an AMF. (A) Effect of field intensity (MNPs concentration of 0.055 g/ml). (B) Effect of MNPs concentration with field intensity of 42.9Gs. MNPs, magnetic nanoparticles; Field intensity of AMF and MNPs concentrations have effect on the inductive heating property of MNPs under AMF exposure. AMF, alternative magnetic field.

Figure 6

Typical temperature curves of the rabbits under MSH (A) Temperatures measured at the rectum and the inner and outer esophageal walls of the rabbits. (B) Temperatures measured at the inner- and outer-side of the esophagus. MSH, magnetic stent hyperthermia.

Figure 7

Pathological change of the normal esophagus following magnetic stent hyperthermia (MSH) treatment (HE staining)

Figure 8

Rabbit esohphageal tumor featured by barium meal and stent implant. (A) Normal rabbit esophagus. (B) Rabbit esohpageal cancer. (C) Implantation of the stent. Arrow, tumor location.

Figure 9

Effect of magnetic stent hyperthermia (MSH; 46°C for 10 min) on tumor volume. MSH using the thermal dose of 46°C for 10 min was able to effectively inhibit the tumor growth in the rabbit esophageal tumor model. MSH, magnetic stent hyperthermia.

Figure 10

Typical temperature curve of the rabbits undergoing magnetic fluid hyperthermia (MFH). The temperature of the rabbit rectum was kept constant during the treatment, confirming the local treatment of MFH.

Figure 11

Effect of magnetic fluid hyperthermia (MFH) on tumor volume. MFH can greatly inhibit the in vivo tumor growth.

Figure 12

Survival rate of tumor-bearing rabbits in the magnetic fluid hyperthermia (MFH), MF and control groups. MFH was able to significantly increase the life span of the tumor-bearing rabbits over that of the control and MNP injection groups.

Figure 13

Pathological changes of rabbit esophageal cancer tissue under various treatments (HE staining). (A) Control (B) MF and (C) MFH groups. MFH, magnetic fluid hyperthermia.