Biomedical Engineering Reference
In-Depth Information
6.4.1.3
MNP s in Hyperthermia and Thermal Ablation
The application of suffi cient heat to kill cells in the treatment of cancer is referred
to as hyperthermia [174, 175], and can be used in combination with conventional
treatment modalities. Although clinical trials have demonstrated the effi cacy of
such combinations [176, 177], the major limitations of hyperthermia have been
the selective targeting and homogeneous distribution of heat within the tumor.
Hyperthermia procedures use different sources of heat within the tissue, includ-
ing externally applied electromagnetic waves (e.g., RF or microwaves), ultrasound
(external or interstitial), a current fl ow between two or more electrodes, electric or
magnetic fi elds between antennas, or electrically or magnetically induced thermo
seeds [176]. The use of biocompatible SPIONs coupled with a magnetic fi eld by
an alternating magnetic fi eld to produce heat due to Brownian and Neel relaxation
processes, is a well-known procedure [139, 178].
Magnetic particles in a range of sizes have been utilized for hyperthermia and
tested on a variety of cancers (mammary, prostate, melanoma, breast, prostate,
glioma) in animal models [179-185] and in a clinical trial [186]. Hyperthermia
treatment depends on the applied temperature, with the duration of heating result-
ing either in direct tumor cell killing or rendering the cells more susceptible to
concomitant radiotherapy or chemotherapy. In recent years, numerous groups
have been developing this area worldwide, with the result that two effi cacy trials
are currently being conducted for glioblastoma multiforme (in combination with
radiotherapy) and prostate cancer (intermediate risk patients, in combination
with low-dose rate brachytherapy). Jordan
et al.
have conducted extensive studies
with MNPs, both in animals and in clinical trials, by using magnetic fl uid - induced
hyperthermia (MFH) [174, 175]. Their study results (Figure 6.10; Table 6.2) have
shown that MFH could be applied to humans (Figure 6.11), the group having
achieved a mean cumulative equivalent minutes (CEM) thermal dose at 43 °C at
the index temperature (T90), in comparison with results reported by other groups
[187-189]. Currently, Phase II clinical trials using MFH are still ongoing [174].
Many new developments are currently under way to improve hyperthermia. One
example is that of tumor-targeting ligands on the surface of iron oxide nanopar-
ticles, which should bind specifi cally to certain tumor cell epitopes or vascular
targeting molecules, or perhaps accumulate in the lymph nodes after systemic
administration. Focused hyperthermia represents another approach, an example
being the
111
In - ChL6 - MAb - conjugated SPIONs (bioprobes) developed by DeNardo
et al.
to target breast cancer cell membrane antigens in mice. Such therapy would
be carried out with an externally applied alternating magnetic fi eld ( AMF ) so as
to deliver thermoablative cancer therapy [139, 178] . AMF - responsive bioprobes
have enabled specifi c cancer cell thermal ablation by the selective targeting of
extravascular cancer cells.
Electron microscopy images have confi rmed the presence of bioprobes on the
surfaces of HBT 3477 cells from
ex vivo
tumors; tumor necrosis was observed in
these samples at 24 and 48 h after treatment with AMF/bioprobe therapy (Figure
6.12 ). Signifi cant therapeutic responses were reported, with an up to eightfold
longer mean time to quintuple the tumor volume with therapy compared to no
