The Application of Plant Viral Nanoparticles in Tissue-Specific Imaging - Nanotechnology for Biomedical Imaging and Diagnostics - page 409

considered, with a value of almost 400,000 mM −1 s −1 for SNps. even greater relax-
ivities could be obtained with the more optimal hopo ligand, paving the way for
the use of TMV and other rod-shaped particles as supramolecular Mri contrast
agents [107].
These VNp contrast agents have not yet been applied in vivo , with most evaluations
carried out in test tubes in the laboratory setting. however, opportunities clearly exist
for their translation into the clinic as these VNp constructs have so far been shown to
be safe and biocompatible. There are many possibilities for Gd 3+ incorporation into
VNps: direct binding at the interface between coat protein subunits, covalent attach-
ment to the exterior and interior surface, and complexation with rNA molecules within
the capsid. All these different approaches resulted in formulations with significant
enhancements in relaxivity that are highly promising for future clinical use.

14.7 peT imAging

recently, VNps have also been explored as a carrier of radionuclides for positron
emission tomography (peT) imaging, a noninvasive technique that uses radioiso-
topes that emit positrons when they undergo positive beta decay. peT imaging has
been demonstrated as a valuable tool for evaluating biodistribution, tracking delivery,
and monitoring therapeutic efficacy. The positrons travel a short distance after
emission until they encounter electrons (see chapter 7), at which point the electron-
positron pairs undergo annihilation and produce pairs of photons that travel in
opposite directions. These photons are detected and the location of the annihilation
events reconstructed, with the resulting image displaying where the molecular tracer
has localized. A glucose analog, fluorodeoxyglucose (FDG) labeled with fluorine-18
( 18 F), is the most common radiotracer used in peT imaging because it becomes
localized in regions of high glucose metabolism, an attribute of most cancers. There
are also other advantages of using 18 F, including its relatively long half-life of 110 min
and the high-resolution images that can be obtained due to low-energy positron
scattering (reviewed in ref. [108]).
The preliminary exploration of using VNps with peT imaging exploited these
advantages of 18 F for biodistribution studies. Chemical conjugation to interior
tyrosine residues of MS2 was used to sequester [ 18 F]fluorobenzaldehyde within
the capsid so that the radionuclide would not affect the biodistribution of the native
particle. peT imaging studies were performed to study the in vivo biodistribution
of [ 18 F]-MS2 particles alongside [ 18 F]fluorobenzaldehyde after intravenous injec-
tion in Sprague-Dawley rats. The MS2 particles were able to avoid renal filtration
due to their larger size, indicating that the capsids remained assembled. [ 18 F]
Fluorobenzaldehyde was almost completely cleared through the kidneys within
5 min and collected in the urine, while [ 18 F]-MS2 circulated for at least 3 h and
localized in the liver and spleen (Fig. 14.7a and b).The [ 18 F]-MS2 agents were
further loaded inside with around 50 coumarin fluorophores per particle, and it
was found that the distribution and clearance rate were not affected, verifying the
hypothesis that interior cargos do not significantly alter the biodistribution [109].