14 Medical Applications of Magnetic Nanoparticles
337
where C is the molar concentration of the magnetic center of the CA in mmol/L,
and T i,obs and T i,diam are the relaxation times of the water protons with and without
the magnetic contribution coming from the CAs, respectively [38]. The larger the
difference in the relaxation rates induced by the CA, the higher its efficiency.
MRI CAs are divided in two main categories: paramagnetic and superparamagnetic compounds. Paramagnetic compounds are typically made of lanthanides
or metal ions embedded in an organic shell, as for example Gd-based molecules
[39–41]. Dipolar fluctuating magnetic fields characterize these ions, due to the presence of one or more free electrons. Commercial superparamagnetic compounds are
instead made of a low crystallinity, non-stoichiometric iron oxide core of about 5 nm
diameter coated by polymers or sugars with a total diameter of about 150–200 nm
[42–44]. The particle magnetic moment (also called “superspin”) fluctuates due to
the thermal energy and interacts with the nuclear magnetization of the surrounding
water protons. All these CAs generally present non-specificity and diffuse freely in
the extracellular space.
In the latest years, a lot of attention has been focused on the development of MNPs,
which can be used as multifunctional agents in the biomedical field, including the
capability to work as CAs in MRI [34, 45–51]. These particles are typically made of
an iron oxide magnetic core with mean size lower than 20 nm. Magnetite (Fe 3 O 4 ) and
maghemite (γ-Fe 2 O 3 ) are generally the preferred materials due to their low toxicity
for the body, which has its own metabolic pathways for the iron absorption and
disposal. The very small size is often preferred, since small MNPs better interact
with the cells and remain for a longer time in the bloodstream.
Iron oxide superparamagnetic nanoparticles (SPIO, i.e., superparamagnetic iron
oxides, core size bigger than 50 nm or USPIO, i.e., ultra-small superparamagnetic
iron oxides, core size smaller than 50 nm), could be applied as T 2 * relaxation
enhancing CAs. The susceptibility effects of the iron oxide cores are indeed able
to determine a signal loss and consequently to darken the MR image in the region
where they accumulate, increasing the contrast in the region of interest. T 2 *-weighted
pulse sequences are generally applied to acquire a MR image after SPIO or USPIO
administration to the patient. From a technical point of view, differences between the
T 2 * measured before and after the administration of SPIOs could be correlated to
the concentration of iron in the region of interest. However, the relation among the
amount of SPIOs administered to the region and the T 2 * enhancement obtained in
the image is linear only when the iron concentration is low [52]. It will be possible
to obtain good enhancement in the MR image giving small amounts of SPIOs only
when strong magnetic fields, as the ones used by 7.0 T MRI apparatus, will be
available in the clinical practice. Until then, the iron concentration evaluated by the
measured T 2 * is susceptible to be highly inaccurate. Moreover, this inaccuracy is
increased by the magnetic field inhomogeneities typically unavoidable in an MRI
setup [53–55].
In this framework, the T 2 enhancement was proved by Tong et al. [56] with a
new method for coating and functionalizing superparamagnetic iron oxide nanoparticles with biocompatible DSPE-PEG copolymers. They systematically studied the
337
where C is the molar concentration of the magnetic center of the CA in mmol/L,
and T i,obs and T i,diam are the relaxation times of the water protons with and without
the magnetic contribution coming from the CAs, respectively [38]. The larger the
difference in the relaxation rates induced by the CA, the higher its efficiency.
MRI CAs are divided in two main categories: paramagnetic and superparamagnetic compounds. Paramagnetic compounds are typically made of lanthanides
or metal ions embedded in an organic shell, as for example Gd-based molecules
[39–41]. Dipolar fluctuating magnetic fields characterize these ions, due to the presence of one or more free electrons. Commercial superparamagnetic compounds are
instead made of a low crystallinity, non-stoichiometric iron oxide core of about 5 nm
diameter coated by polymers or sugars with a total diameter of about 150–200 nm
[42–44]. The particle magnetic moment (also called “superspin”) fluctuates due to
the thermal energy and interacts with the nuclear magnetization of the surrounding
water protons. All these CAs generally present non-specificity and diffuse freely in
the extracellular space.
In the latest years, a lot of attention has been focused on the development of MNPs,
which can be used as multifunctional agents in the biomedical field, including the
capability to work as CAs in MRI [34, 45–51]. These particles are typically made of
an iron oxide magnetic core with mean size lower than 20 nm. Magnetite (Fe 3 O 4 ) and
maghemite (γ-Fe 2 O 3 ) are generally the preferred materials due to their low toxicity
for the body, which has its own metabolic pathways for the iron absorption and
disposal. The very small size is often preferred, since small MNPs better interact
with the cells and remain for a longer time in the bloodstream.
Iron oxide superparamagnetic nanoparticles (SPIO, i.e., superparamagnetic iron
oxides, core size bigger than 50 nm or USPIO, i.e., ultra-small superparamagnetic
iron oxides, core size smaller than 50 nm), could be applied as T 2 * relaxation
enhancing CAs. The susceptibility effects of the iron oxide cores are indeed able
to determine a signal loss and consequently to darken the MR image in the region
where they accumulate, increasing the contrast in the region of interest. T 2 *-weighted
pulse sequences are generally applied to acquire a MR image after SPIO or USPIO
administration to the patient. From a technical point of view, differences between the
T 2 * measured before and after the administration of SPIOs could be correlated to
the concentration of iron in the region of interest. However, the relation among the
amount of SPIOs administered to the region and the T 2 * enhancement obtained in
the image is linear only when the iron concentration is low [52]. It will be possible
to obtain good enhancement in the MR image giving small amounts of SPIOs only
when strong magnetic fields, as the ones used by 7.0 T MRI apparatus, will be
available in the clinical practice. Until then, the iron concentration evaluated by the
measured T 2 * is susceptible to be highly inaccurate. Moreover, this inaccuracy is
increased by the magnetic field inhomogeneities typically unavoidable in an MRI
setup [53–55].
In this framework, the T 2 enhancement was proved by Tong et al. [56] with a
new method for coating and functionalizing superparamagnetic iron oxide nanoparticles with biocompatible DSPE-PEG copolymers. They systematically studied the