Thermal ablation of tumors using magnetic nanoparticles: an in vivo feasibility study

Abstract

Rationale and objective: Feasibility of a new interventional procedure for the treatment of breast cancer called "magnetic thermal ablation" was examined under in vivo animal conditions. The method consists in the intratumoral application of iron oxide particles and the exposure of the breast to an alternating magnetic field, whereby the tumor is eliminated by heat.

Materials and methods: Human breast adenocarcinomas were implanted into 45 immunodeficient SCID mice. Defined magnetite particle masses (between 4 mg and 18 mg per 100 mg tumor tissue) were injected intratumorally. Approximately 20 minutes later, animals were exposed to an alternating current (AC) magnetic field (amplitude: 6.5 kA/m, frequency: 400 kHz) for 4 minutes while measuring the temperature at defined tumor positions and at the rectum. The method efficacy was determined by the following end points: the assessment of the deposited heat dosages (DHD) at the defined locations within the target. The DHD was defined as the area between the time-dependent temperature curves during treatments and the temperature level without heating; histologic examinations of tumor tissue after heating; and the evaluation of the particle wash-out from the tumor by determining the percentage of injected iron doses per g tissue of selected organs (atomic absorption spectrometry; 50 minutes postinjection).

Results: Temperature increases between 12 degrees C and 73 degrees C were registered at different tumor locations (tumor center and periphery). The corresponding DHD ranged between 40 degrees C and 262 degrees C x minutes. Regions of DHD underdosage (lower than approximately 47-61 degrees C x min) were observed in 8 of 36 tumors. 2.4% to 22.3% of the injected iron dose per g dried tissues other than the tumor was detected after 50 minutes postinjection. Histologic examinations showed the presence of early stages of coagulation necrosis in treated tumor cells.

Discussion and conclusion: The data indicate that the proposed method allows the generation of localized heat spots at the tumor area. According to the histologic analysis and previous investigations the DHD were, in principle, high enough to kill tumor cells. The reasons for the presence of regions of temperature underdosage are discussed in the text. Special attention should be paid on the particle wash out in organs in the vicinity of the breast.