Animal Models for Preclinical Imaging - Nanotechnology for Biomedical Imaging and Diagnostics - page 462

use survival curves to assess response to therapy or external measurement of subcu-
taneous xenograft size by caliper measurements. Imaging enables noninvasive mea-
surements in orthotopic cancer studies and internal pathologies.

16.4.1 Animal models for imaging Arthritis and inflammation

Arthritis affects nearly all people at some point in their lives due to the natural
aging process. other forms of arthritis develop in younger people due to injuries,
autoimmune disease (rheumatoid arthritis (RA)), and genetic disorders affecting
cartilage growth or joint conformation (e.g., hip dysplasia). Diagnosis of arthritis
must include determining the etiology of the joint pain to select the appropriate
treatment. While these diseases have been known for many years, the complex
mechanisms that result in damage have not been elucidated fully, and more investi-
gation is needed.
Arthritis describes a broad range of diseases that cause inflammation and pain of
the joints. The most common models for inflammation requires direct injection
of irritants.
Arthritis was induced in rabbits by intra-articular injection of albumin and
scanned with BolD MRI periodically for 28 days [6]. Inflammation of the joint
(synovitis) was specifically detected compared with control (untreated and saline
injected). Animal models have been used in the development of pharmaceuticals
prior to use in humans. Arthritis may be induced by chemical or other injury
directly to the joints, systemic arthritis-inducing drugs, or genetic engineering of
animals to mimic human disease.
Inflammation results in dilation of blood vessels, vascular leakiness, and infiltra-
tion of tissue with white blood cells. Thus, inflammation is an obvious choice for
optical imaging with fluorescent contrast agents that accumulate nonspecifically due
to enhanced permeability and retention (EPR). This can give a better measurement of
inflammation than traditional measures of swelling, particularly at early time points.
It also allows more sensitive measurement with less inflammation needed to see a
response. Fluorescence imaging can be used to measure the relative reduction in
inflammation due to pharmaceutical intervention. It can also be used to measure
molecular markers of inflammation associated with diseases such as cancer, cardio-
vascular disease and others.
Animal models have also been used extensively in basic research to study the
genetic predispositions to arthritis and immunology of RA. RA is an autoimmune
disease that affects all the joints of the body and can occur at any time of life. To
date, there has been limited success in treatment due to poor efficacy over time or
adverse side effects at effective doses. Animal models of RA have been predictive
of outcomes in humans. Adjuvant-induced arthritis models are produced by
intradermal injection of immune-stimulating compounds such as Freund's complete
adjuvant (FCA) including mycobacterium, synthetic adjuvant, or type II collagen
(typically bovine).
osteoarthritis (oA) is a degenerative disease of the joints that affects the cartilage
and bone and is diagnosed by symptoms, X-ray radiography, and CT. Generally, X-ray