14 Medical Applications of Magnetic Nanoparticles
345
to other medical imaging techniques, which allow the collection of similar information typically by using X-rays and appropriate opaque contrast agents injected into
the blood vessels (i.e., fluoroscopy). The USPIO iron-based MRI CA Ferumoxytol
is commonly used to produce enhancedT 1 -weighted MR images of blood vessels,
since it has a 14–15 h long intravascular half-life, allowing imaging to be repeated
from the early arterial phase to the later ones with high signal-to-noise ratio and
resolution [108–114].
SPIO-based CAs can be used to evaluate inflammatory responses in the human
body, which can be caused by tumors or other serious diseases such as diabetes,
atherosclerosis, multiple sclerosis and so on. All the inflammatory processes involve
macrophages, whose tendency is to incorporate SPIOs. A first example of application
of SPIOs for MR evaluation of inflammatory processes is the case of type-1 diabetes
patients, which is strictly correlated to a pancreatic inflammation. A totally new
approach based on SPIOs, and particularly on Ferumoxytol, described by Gaglia
et al. [121], exploits SPIOs uptake by macrophages in the inflamed pancreatic region
to obtain an enhancement in the MR image.
Another application of USPIOs and SPIOs is the diagnosis of atherosclerosis,
and particularly the identification of high-risk atherosclerotic plaques. USPIOs (as
Ferumoxtran-10) exploit the dysfunctional endothelium typical of atherosclerotic
plaques to penetrate the macrophage-rich inflamed region, where they induce a MRI
signal loss, allowing to differentiate among symptomatic and asymptomatic patients.
Unlikely MRI, where the use of MNPs is a routinely clinical practice, their application as heat mediators in tumor therapy by MFH is still at its infancy. Feasibility and
efficacy of single or recursive MFH treatments of several kinds of cancers (glioblastoma, mammary and prostate carcinoma) by local MNPs injection have been demonstrated on animal models since the last decade of the 1900s.[122–125]. Concerning
translation to humans, a first clinical application of interstitial MFH using MNPs
for treating a patient with previously irradiated and locally recurrent prostate carcinoma was carried out by Johannsen et al. in the early 2000s [126]. After this pilot
study, that demonstrated how MFH was feasible and well-tolerated, clinical trials on
patients with glioblastoma multiforme, prostate, esophagus, and liver cancers were
performed to investigate the potentiality of MFH [127–129]. MFH experimental
applications and systematic clinical studies have been performed by Jordan et al.
[127, 130–132] on patients suffering from glioblastoma multiforme, prostate and
pancreas tumors. Since 2010, when MagForce company (https://www.magforce.de/
en/home.html) presented the first prototype able to host a whole human body [133],
a magnetic field applicator (NanoActivator
® ), operating with alternating magnetic
field of 2–15 kA/m amplitude and 100 kHz frequency, is in current use at Charité
Hospital in Berlin for treatment of glioblastoma.
Nowadays the NanoTherm
® therapy has been clinically tested or is under clinical
evaluation in other hospitals both in Europe and in the Unites States. At present the
therapy has been applied on 90 patients suffering from brain cancer and 80 patients
affected by inter alia, pancreatic, prostate, breast and oesophageal tumor were treated
as part of a pilot study. The therapy procedure consists in the direct injection in the
tumor mass of a high dose (ca. 30 mg per cm
3 of tissue) of NanoTherm
® , a suspension
345
to other medical imaging techniques, which allow the collection of similar information typically by using X-rays and appropriate opaque contrast agents injected into
the blood vessels (i.e., fluoroscopy). The USPIO iron-based MRI CA Ferumoxytol
is commonly used to produce enhancedT 1 -weighted MR images of blood vessels,
since it has a 14–15 h long intravascular half-life, allowing imaging to be repeated
from the early arterial phase to the later ones with high signal-to-noise ratio and
resolution [108–114].
SPIO-based CAs can be used to evaluate inflammatory responses in the human
body, which can be caused by tumors or other serious diseases such as diabetes,
atherosclerosis, multiple sclerosis and so on. All the inflammatory processes involve
macrophages, whose tendency is to incorporate SPIOs. A first example of application
of SPIOs for MR evaluation of inflammatory processes is the case of type-1 diabetes
patients, which is strictly correlated to a pancreatic inflammation. A totally new
approach based on SPIOs, and particularly on Ferumoxytol, described by Gaglia
et al. [121], exploits SPIOs uptake by macrophages in the inflamed pancreatic region
to obtain an enhancement in the MR image.
Another application of USPIOs and SPIOs is the diagnosis of atherosclerosis,
and particularly the identification of high-risk atherosclerotic plaques. USPIOs (as
Ferumoxtran-10) exploit the dysfunctional endothelium typical of atherosclerotic
plaques to penetrate the macrophage-rich inflamed region, where they induce a MRI
signal loss, allowing to differentiate among symptomatic and asymptomatic patients.
Unlikely MRI, where the use of MNPs is a routinely clinical practice, their application as heat mediators in tumor therapy by MFH is still at its infancy. Feasibility and
efficacy of single or recursive MFH treatments of several kinds of cancers (glioblastoma, mammary and prostate carcinoma) by local MNPs injection have been demonstrated on animal models since the last decade of the 1900s.[122–125]. Concerning
translation to humans, a first clinical application of interstitial MFH using MNPs
for treating a patient with previously irradiated and locally recurrent prostate carcinoma was carried out by Johannsen et al. in the early 2000s [126]. After this pilot
study, that demonstrated how MFH was feasible and well-tolerated, clinical trials on
patients with glioblastoma multiforme, prostate, esophagus, and liver cancers were
performed to investigate the potentiality of MFH [127–129]. MFH experimental
applications and systematic clinical studies have been performed by Jordan et al.
[127, 130–132] on patients suffering from glioblastoma multiforme, prostate and
pancreas tumors. Since 2010, when MagForce company (https://www.magforce.de/
en/home.html) presented the first prototype able to host a whole human body [133],
a magnetic field applicator (NanoActivator
® ), operating with alternating magnetic
field of 2–15 kA/m amplitude and 100 kHz frequency, is in current use at Charité
Hospital in Berlin for treatment of glioblastoma.
Nowadays the NanoTherm
® therapy has been clinically tested or is under clinical
evaluation in other hospitals both in Europe and in the Unites States. At present the
therapy has been applied on 90 patients suffering from brain cancer and 80 patients
affected by inter alia, pancreatic, prostate, breast and oesophageal tumor were treated
as part of a pilot study. The therapy procedure consists in the direct injection in the
tumor mass of a high dose (ca. 30 mg per cm
3 of tissue) of NanoTherm
® , a suspension