Nanoparticles for Bioimaging: Analytical Characterization and Measurements - Nanotechnology for Biomedical Imaging and Diagnostics - page 166

The relaxivity of an MRI contrast agent is measured by recording the relaxation
times ( T 1 and T 2 ) at different concentrations of the agent. The relaxation times are
converted into relaxation rates ( R 1,2 = 1/ T 1,2 ) and plotted against the concentration. a
linear fit of relaxation rate versus concentration yields a line with a slope corresponding
to the relaxivity in terms of mM −1 s −1 . Relaxivity can be measured relative to the metal
concentration (gadolinium or iron) or the concentration of the carrier molecule
(peptide, particle, liposome, etc.). The relaxivity value is dependent on several exper-
imental factors, including the B 0 field strength, temperature, and medium. These con-
founding factors can make it difficult to compare relaxivity values reported by
different laboratories using various experimental conditions. oftentimes, the relaxiv-
ity of a novel contrast agent is compared with a clinically available standard, such as
gd-DTPa (for paramagnetic agents) or feridex (for iron oxide agents), in order to
provide a normalizing value that can be reproduced at other labs.
Iron oxide nanoparticles have very high T 2 relaxivities, about 5-10 times higher
than their T 1 relaxivity [9-13]. Therefore, they are typically detected as a loss of
signal on T 2 -weighted MRI. a number of physical and chemical properties can
influence the relaxivity of iron oxide nanoparticles, such as the particle size or sur-
face coating [14]. Particles with increasing diameters (3, 4, 5, and 6 nm) display a
progressive increase in the T 2 relaxivity (29, 42, 48, and 61 mM −1 s −1 ). Modification
of the particle surface with a polymer coating increases the T 2 relaxivity of a 6 nm
iron oxide nanoparticle from 61 to 119 mM −1 s −1 .
gadolinium is a paramagnetic metal that has been used extensively in MRI con-
trast agents. Paramagnetic metals generally display similar T 1 and T 2 relaxivities.
Since T 1 relaxation times in the body tend to be much longer than T 2 relaxation times,
these metals typically produce a more apparent shortening of T 1 . Therefore, they are
often used to generate increased signal intensity on T 1 -weighted MRI. gadolinium
agents have been grafted onto a wide range of nanoparticle constructs, including
liposomes, micelles, dendrimers, polymers, viral particles, and liquid perfluorocar-
bon (PfC) particles. a wide variety of factors can influence the relaxivity of para-
magnetic contrast agents, including the size of the particle carrier, the number of
gadolinium ions on each particle, binding to a biological target, or the accessibility
of water to the gadolinium.
Several reports have demonstrated that PfC nanoparticles can be formulated with
gadolinium chelates for MRI detection [15, 16]. anchoring the gadolinium onto a
nanoparticle carrier can improve the relaxivity of the contrast agent via two mecha-
nisms. first, the relatively large size of the particle slows the tumbling rate of the
metal, improving the chemical interaction between the gadolinium ion and the sur-
rounding water molecules. as a result, the relaxivity of gd-DTPa at 1.5 T increases
from 4.5 mM −1 s −1 when diluted in water [17] to 17.9mM −1 s −1 when incorporated
onto PfC nanoparticles [18]. Second, utilizing a nanoparticle allows multiple copies
of the gadolinium chelate to be loaded onto a single carrier, effectively multiplying
the paramagnetic effect induced in the target tissue each time a particle binds to the
biomarker of interest. PfC nanoparticles can be loaded with nearly 100,000 gd-DTPa
molecules per particle, leading to an overall relaxivity of 1,690,000 mM −1 s −1 at 1.5 T
[18]. With such a high relaxivity, the minimum concentration of PfC nanoparticles