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Mammalian vectors such as the aforementioned, however, bear at least
the theoretic potential to revert to a pathogenic state. Therefore, employing
bacteriophages or plant VNPs in targeting strategies becomes an attractive
option. The power of phage-display-mediated targeting to vascular ligands
has also been paired with the genome integration functions of AAV to
result in particles that are an interesting hybrid between classic gene
delivery and nanotechnology approaches. An AAV-targeting vector was
packaged within a targeted fd bacteriophage to achieve tissue-specific gene
Figure 8.11
Targeted AAV vector-mediated molecular imaging of tumor-bearing
mice. (a)
bioluminescent imaging (BLI) of luciferase (Luc) expression after
systemic AAVP delivery (AAVP denotes a specifically engineered version of AAV, the
reader is referred to the original paper, see reference below). Nude mice bearing
DU145-derived tumor xenografts received an intravenous single dose of either RGD-
4C AAVP-Luc or controls (non-targeted AAVP-Luc or scrambled RGD-4C AAVP-Luc).
Ten days later, BLI of tumor-bearing mice was performed. (b) Multitracer PET imaging
in tumor-bearing mice after systemic delivery of RGD-4C AAVP-HSVtk. HSVtk =
In vivo
Herpes
simplex virus
thymidine kinase, a reporter gene that can serve for imaging when
used in combination with radiol-labeled nucleosides [
F]FEAU or as a suicide gene
when used in combination with the prodrug ganciclovir (GCV). Nude mice bearing
DU145-derived tumor xenografts (
18
= 9 tumor-bearing mice per cohort) received an
intravenous single dose of RGD-4C AAVP-HSVtk or non-targeted AAVP-HSVtk. PET
images with [
n
18
F]FEAU obtained before and after GCV treatment are presented. T,
tumor; BL, bladder. Calibration scales are provided in (a) and (b). Superimposition of
PET on photographic images of representative tumor-bearing mice was performed to
simplify the interpretation of [
F]FEAU biodistribution. Reproduced with permission
from Hajitou, A., Trepel, M., Lilley, C. E., Soghomonyan, S., Alauddin, M M., Marini, F.
C., 3rd, Restel, B. H., Ozawa, M. G., Moya, C. A., Rangel, R., Sun, Y., Zaoui, K., Schmidt,
M., von Kalle, C., Weitzman, M. D., Gelovani, J. G., Pasqualini, R., and Arap, W. (2006) A
hybrid vector for ligand-directed tumor targeting and molecular imaging,
18
Cell
,
125
(2),
385-398.
 
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