The Application of Plant Viral Nanoparticles in Tissue-Specific Imaging - Nanotechnology for Biomedical Imaging and Diagnostics - page 411

found that coencapsulation of 18 F-fluoride with the cation poly-L-lysine (pLL)
and ferumoxides resulted in more efficient packaging of the radiotracer. innate bio-
distribution in rats was studied using peT imaging, and similar results were found
as for MS2, with greater accumulation in the liver and spleen for animals injected
intravenously with the hVJ-e formulation. Magnets placed externally on top of the
head were able to alter the biodistribution, guiding the hVJ-e particles to accumu-
late in the head. These results demonstrate the use of combining viral imaging
agents with external stimuli for region-specific delivery and with peT to study the
fate of nanoparticles in vivo [111].
The power of peT imaging has also been harnessed in a different manner as a
method to track the progress of gene delivery. recombinant adeno-associated virus
(AAV) was combined with a filamentous phage derived from M13, fd-tet, to form a
chimeric AAV/phage (AAVp). in this approach, the fd-tet bacteriophage had incor-
porated within its genome cis -elements from AAV's genome to improve integration
of the transgene after delivery to tumor cells. Targeted delivery was achieved using
an rGD motif displayed on the phage's exterior, which binds to integrin receptors
overexpressed in many tumor types. To confirm successful gene delivery to the
tumor, peT imaging of a [ 18 F]2′-fluoro-5-ethyl-1-beta-D-arabinofuranosyluracil
(FeAU) tracer for detection of herpes simplex virus thymidine kinase (hSVtk)
reporter gene expression and bioluminescent imaging of a luciferase reporter gene
were used (Fig. 14.7c and d). in addition, hSVtk served as a suicide gene, with cell
death triggered by administration of ganciclovir (GCV). After GVC therapy, there
was a marked decrease in [ 18 F]FeAU and [ 18 F]FDG accumulation at the tumor site,
indicating cell death and successful suppression of tumor growth (Fig. 14.7d) [110].
Although this is a relatively young discipline, there is great potential for applica-
tions of VNps in peT imaging. Multimodal VNp formulations have been established
that combine peT tracers with targeting and other imaging modalities. Consequently,
there are immense possibilities that exist for the development of innovative new
imaging and therapeutic technologies.

14.8 fuTure ouTlook

The use of VNps for imaging is an emerging discipline, and several promising
approaches have been taken that will lay the groundwork for future applications. For
example, one can take advantage of the interaction between CpMV and vimentin for
imaging vascular disease and tumor angiogenesis. VNps that passively and actively
target cancer cells can be designed as probes for the detection of solid tumors and
sites of metastasis. There is also work underway for the application of VNps for Mri
and peT imaging. Several novel high relaxivity and sensitivity Mri contrast agents,
as well as peT tracers, are being designed for biodistribution, disease metabolism,
and therapeutic efficacy studies.
Going forward toward clinical translation, it will be important to assess the
long-term fate of VNps in vivo . Although numerous novel viral nanoparticulate
systems have been developed, they have not yet been thoroughly investigated