Animal Models for Preclinical Imaging - Nanotechnology for Biomedical Imaging and Diagnostics - page 470

invasion [25]. The ability to follow the infection and visualize its ability to weaken the
BBB will help to understand the pathogenesis of the infection and lead to faster and
more efficient means of treating C. albicans infections.
Aspergillus fumigatus is also reported to be a significant pathogen in immunocom-
promised patients causing high mortality. Infections are difficult to identify due to the
lack of rapid screening tests, and early diagnoses go undetected. Ribosomal RNA
(rRNA) targeting using oligonucleotide probes has been used to identify bacterial
pathogens in vitro and a 99m Tc-labeled phosphorodiamidate morpholino (MoRF)
oligomers (a DNA analog) targeting fungal rRNA [26]. A recent report used this tar-
geting method for imaging detection of fungal infections in mice with A. fumigatus
pulmonary infections.
16.4.4.3 Viral Infection The ability to image progression or regression of viral
infections would greatly benefit the development of vaccines and antiviral therapy
and would contribute to the understanding of the pathogenesis of the viruses.
Some viral infections can be imaged by the manipulation of viral DNA to include
fluorescent or bioluminescent reporters (poxviruses) or by loading viral particles
with other contrast agents. The recombinant virus is expected to replicate and encode
the bioluminescent reporter into oncoming generations. This process could help
visualize viral reproduction and host response simultaneously and provide insight
into the pathogenesis of the virus along with the process of its replication [27].
In addition, there are reports of a well-known PET radiotracer, 18 F-FDG, showing
the ability to visualize inflammatory response processes [28]. The radiotracer is taken
up by cells, phosphorylated and selectively trapped within cells with high rates of
glycolysis. The inflammatory response of both infectious and noninfectious disease
is visualized as the radiotracer is taken up nonspecifically by both lymphocytes and
neutrophils. Theoretically, FDG PET can be used to measure the inflammatory response
of viral infections and provide an understanding of whether or not anti-inflammatory or
antiviral therapies are beneficial.
Bioluminescence imaging using luciferase has recently been an effective imaging
tool following the transmission of viral infections. Using luciferase, murine gamma-
herpesvirus-68 (MVH-68) can be traced from nasal inoculation to vaginal excretion
in a female mouse; however, it was dependent on the presence of estrogen [29]. The
virus is not transmitted to the litter, but direct transmission to a naïve male mouse is
possible. The sexual transmission of MHV-68 to the male mouse has been docu-
mented in the laboratory using bioluminescence imaging, which could lead to a
greater depth of understanding of the disease as well as development of strategies for
preventing spread in a population.
Influenza A is a viral respiratory disease that can cause serious disease worldwide.
The virus's ability to have a segmented genome allows for reassortment between
human, avian, and swine strains and can lead to new pandemic strains [30]. luciferase
can be transgenically implemented into influenza A so that it will encode it into inser-
tion sites of host cells. This will allow for real-time observations of the virus as it
spreads, as well as give insight into how monoclonal antibodies interact for therapeutic
analysis.