Animal Models for Preclinical Imaging - Nanotechnology for Biomedical Imaging and Diagnostics - page 466

16.4.2.4 Orthotopic Xenografts These models can be produced similarly by injec-
tion of cells or implantation of tumor tissues in the equivalent location in the mouse.
Implantation of breast cancer cells in the mammary tissue of mice results in faster
growth and histology more like human breast cancer. It is believed that the cancer cells
are better suited to the environment from which they originated, contributing to. the
“seed and soil” hypothesis.
16.4.2.5 Metastatic Models Cancer metastasis can also be modeled through injec-
tion of cells into locations for delivery to other places. For example, a well-studied
model of breast cancer metastasis to the bone marrow is by intracardiac injection of
human breast cancer cells. Another example is ovarian cancer that frequently forms
abdominal metastases. This disease process has been modeled by intraperitoneal
injection of ovarian carcinoma cells. Metastases to the brain, lungs, lymph nodes, and
liver have also been modeled in a similar manner. These models have contributed
significantly to the “seed and soil” hypothesis as well as the reseeding hypothesis.
16.4.2.6 Human Tissue Explants Implantation of intact tissues has demon-
strated even greater advantage for replicating the biology of human disease. Intact
tissues freshly collected from human cancer patients during surgery are implanted in
immunocompromised mice. In the original human-in-mouse breast cancer model,
the mammary fat pad is cleared and replaced with human fibroblasts before insertion
of breast cancer tissue removed from human patients. The goal of this model is to better
replicate the biology of human breast cancer. Researchers have compared the histology,
genetics, and molecular expression patterns of primary and metastatic human cancer to
the transplanted tumors. In general, the transplanted tumors maintained similar biology
and gene expression to the original tumor, but in some cases, gene expression better
correlated with that of metastases.
16.4.2.7 Spontaneous and Transgenic Models Genetic predisposition to cancer
development has been found in certain lines of mice, rats, and other animals. These
models replicate natural cancer development in the respective organ. Such models
are relatively specific in type and have long latency, which is a limitation for most
imaging studies.
Transgenic models have been developed by genetic modification of host DNA to
introduce oncogenes or eliminate tumor suppressor genes. These animal models
were initially developed to investigate causative factors in cancer development. Many
transgenic cancer models develop tumors in relatively short time and in predictable
manner. For example, the mouse mammary tumor virus (MMTV) gene selectively
affects the mammary tissues and can be altered to include oncogenes such as HER2/
neu and PyMT. Hemizygous MMTV-PyMT model predictably develops multifocal
tumors throughout the mammary tissues at 8-12 weeks.
16.4.2.8 Viral-Induced Cancer Viral-induced cancers are known in animal
models. Viruses can be genetically engineered to locally introduce desired DNA
leading to cancer development. This reverse of gene therapy can be beneficial for