Nanoparticles for Bioimaging: Analytical Characterization and Measurements - Nanotechnology for Biomedical Imaging and Diagnostics - page 167

required for MR image detection, defined as the concentration required to produce a
contrast-to-noise ratio of 5, is around 100 pM at a typical clinical field strength (1.5 T)
and 25pM at a higher field strength used for high-resolution imaging in animal
research (4.7 T) [18]. The advantages of coupling numerous paramagnetic chelates
onto a nanoparticle carrier have also been described for micelles [19], dendrimers [20],
liposomes [21, 22], and other particle systems.
The relaxivity of a contrast agent can change when the molecule binds to a
biological target. for example, aBlaVaR is an MRI contrast agent approved for use
in angiography that binds to albumin in the blood pool. When aBlaVaR binds to
albumin, the relaxivity increases by a factor of five compared to other clinical con-
trast agents [23]. In a similar manner, EP-2104R is a contrast agent that binds to
fibrin in clots [24]. The relaxivity of EP-2104R is 11.1mM −1 s −1 in solution but
increases to 24.9 mM −1 s −1 when bound to a fibrin clot [25, 26].
Some MRI contrast agents are specifically designed to alter their relaxation
behavior based on environmental conditions, such as temperature [27], pH [28], oxy-
genation [29], ion concentration [30, 31], or enzyme activity [32, 33]. These effects
are often achieved by developing an agent that alters its chemical structure based on
the local conditions. These conditions can alter the molecular bonds or relative posi-
tion of chemical groups, changing the accessibility of water to the metal. alternatively,
agents have been designed to bind to plasma proteins or cluster together only in the
presence of certain ions or enzymes, yielding a dramatic increase in their relaxivity
under these conditions.
liposomes have been designed to selectively release an encapsulated payload
upon thermal activation. The payload could be a therapeutic drug and/or an MRI con-
trast agent for visualizing liposome permeability. a thermosensitive liposome that
encapsulated a clinical gadolinium contrast agent displayed a very small T 1 relaxivity
of 0.5 mM −1 s −1 at low temperatures [34]. The relaxivity quickly rose to 3 mM −1 s −1 as
the temperature increased between 40 and 43°C, but did not change further up to
50°C. These results demonstrate that the liposome membrane rapidly becomes very
porous at 40-43°C, allowing controlled release of the encapsulated payload.
Many factors play into the in vivo compatibility and utility of MRI contrast agents
based on nanoparticle carriers. The chemical composition of the particle system can
drastically affect the toxicity, biodistribution, elimination rates, and stability of MRI
contrast agents. furthermore, the metal content, particle size, metal loading, and water
interaction can impact the relaxivity of the contrast agent. Both the biocompatibility
and MRI visibility need to be optimized for in vivo detection of the contrast agent. If the
nanoparticle is designed to specifically target a biomarker to achieve molecular imaging
of disease, the targeting agent must also display high affinity for the selected target and
minimal binding to other cellular components. Nanoparticle-based MRI contrast agents
have been developed to take advantage of the high payload ability and long circulation
time to home to pathological tissues, such as tumors, atherosclerotic plaques, myocardial
infarctions, etc. These agents offer great promise for noninvasive tracking of disease
progress and/or therapeutic effects. Ultimately, the clinical application of selectively
targeted MRI contrast agents could be used to improve patient outcomes in a wide
variety of the most pressing healthcare challenges facing society as a whole.