Animal Models for Preclinical Imaging - Nanotechnology for Biomedical Imaging and Diagnostics - page 463

and CT cannot detect pathology of the cartilage or synovia. Soft tissue (cartilage,
ligaments, tendons) defects are best observed with MRI; however, contrast
enhancement, such as microCT arthrography, and other special techniques can elu-
cidate more information about the status of disease detected by MRI. oA develops
from increased friction and wear of the joint as a result of joint incongruity, laxity, or
injury or age-related wear. oA can cause significant pain and generally gets worse
with time unless cause can be eliminated through joint resurfacing or replacement.
Drug development for oA has been very successful in managing oA-related pain.
However, at this time, there are no drugs that have successfully demonstrated repair
of cartilage defects and reduction of oA. Further investigation into the pathophysi-
ology of oA and mechanism for regenerating synovial cartilage is needed to improve
outcomes in patients with oA.
Certain strains of guinea pig develop spontaneous oA of the knee that can be
detected by CT at 11 months [7]. Intra-articular injection of mono-iodoacetate (MIA)
induces oA-like pathology by interfering with cartilage metabolism [8, 9]. While
commonly used as a model of inflammation, injection of FCA or N,N -dioctyldecyl-
N ', N -bis(2-hydroxyethyl)propanediamine (lA) suspended in oil in the hind paw of
rats results in oA of the joints of that foot [10]. Glucose-6-phosphate isomerase-
induced arthritis was imaged with 18 F-FDG PET/CT (Fig. 16.3) [11].
Paw edema can be induced by intraplantar injection of 10 µl of 10 mg/ml
β-zymosan in sterile 0.9% NaCl solution and followed by molecular imaging of
cathepsin activity using activatable and affinity-based fluorescent contrast agents
[12]. Molecular imaging methods are also used to detect cells and molecular markers
of inflammation associated with specific diseases. Thus, surgical models of oA have
been developed to mimic injury-related oA. These include direct cartilage injury [9]
and destabilization of the medial meniscus [13].

16.4.2 Animal models for cancer imaging

Cancer, in particular, is a disease amenable to imaging for diagnosis as it usually
does not produce definitive signs at an early stage. Breast cancer screening through
mammography has significantly improved outcomes in women through early detec-
tion and therefore better prognosis. Cancer diagnosis is generally determined by
imaging through anatomical abnormalities induced at the primary site and some-
times in distant locations at late stages. This imaging guides surgical therapy and is
used to monitor the progress of neoadjuvant, adjuvant, and radiation therapy. The
majority of preclinical cancer research models are murine due to the variety of strains
available and repeatability. Some common types of mouse models used in biomed-
ical research are shown in Figure 16.4.

16.4.2.1 Spontaneous Cancer Models Cancer occurs naturally in many animals,
with the wide variety seen in the human counterpart. like the human disease, spontaneous
cancer occurrence is generally unpredictable and with long latency. Certain lines of mice
and rats more predictably develop tumors.