VNPs as Tools for Nanomedicine - Viral Nanoparticles: Tools for Materials Science and Biomedicine - page 219

Combined with targeting molecules to achieve destination-specific
imaging these VNPs would be a powerful tool for non-invasive detection and
visualization of disease and progression. Furthermore, optimization of the
system, such as the use of near-infrared (NIR) probes, is expected to improve
sensitivity. The feasibility of using CPMV for NIR fluorescence tomography
has also been demonstrated (Wu et al ., 2005).

.. VnPs as Contrast Agents for MrI

MRI provides a powerful non-invasive imaging tool and is one of the most
frequently utilized techniques for

imaging. MRI is based on the
alignment of protons from hydrogen atoms in a strong magnetic field.
The aligned protons are then exposed to a pulse of radio waves, which
leads to absorption of energy. When the second field is turned of, energy
is released and can be detected by the scanner to generate the MRI image.
Contrast agents are typically used to increase the brightness of the image
and hence sensitivity of the technique. The principle of contrast agents is to
increase relaxation time of water protons, the process by which the nuclear
magnetization (alignment of protons) returns to equilibrium distribution.
Gadolinium (Gd

in vivo

3+

) is commonly used as a contrast agent (reviewed in Aime

et al ., 2002). Enhanced relaxivities can be achieved by coupling the contrast

agent (Gd ) to a macromolecular carrier such as dendrimers or liposomes

(Immordino

3+

., 2006; Kobayashi & Brechbiel, 2005).
More recently, VNPs including CPMV, CCMV, MS2, and Q

et al

have been
found to be promising platforms for contrast agent development (reviewed
in Liepold

b

., 2007). VNPs are rigid structures with large rotational
correlation times, resulting in increased relaxivity. In addition, because
of the polyvalent nature of VNPs several hundred Gd

et al

molecules can be
complexed or attached to the VNP. It has been shown that Gd

3+

molecules
can be covalently attached to the exterior or interior surface, complexed
with encapsidated RNA molecules, or bound at intrinsic metal-binding sites
at coat protein interfaces (Allen

3+

et al ., 2005; Anderson et al ., 2006; Hooker

et al ., 2007) (recall Chapters 4 and 5 with regard to

the attachment strategies). Each of these paramagnetic VNP formulations
exhibited extraordinarily high relaxivities, indicating that VNPs could serve
as excellent candidates for MRI contrast agents. An

., 2007; Prasuhn et al

in vivo evaluation of the

performance of the materials has not yet been reported.