Animal Models for Preclinical Imaging - Nanotechnology for Biomedical Imaging and Diagnostics - page 457

investigation of biological processes relevant to human disease. They can be separated
into (i) development of novel imaging techniques, (ii) development of therapeutic and/
or diagnostic agents, and (iii) reporting of protein and gene expression.
As the theme of this topic is nanomaterials in biomedical imaging, this chapter
will focus on relevant animal models that require only basic animal handling and
surgical skills used in most research institutions. It is not in the scope of this single
chapter to elaborate on all animal models available at this time, but to present a
survey of animal models that broadly reflect the biology of human disease suffi-
ciently for molecular imaging with nanomaterial contrast agents. Rodent models
are most prevalent in biomedical research for practical and economic reasons and
will encompass the most attention.

16.2 ethics in AnimAl reseArch

The use of animals in research has provided immeasurable benefit to our understanding
and ability to treat human disease. While significant progress has been made in the
development of alternatives to animals in research, the progression of disease, delivery of
diagnostic and therapeutic agents, and response to therapies cannot be adequately evalu-
ated by in vitro assays. Regardless of scientific impact, preclinical imaging studies should
always be designed with respect for animal life and to minimize any pain and suffering.
local Institutional Animal Care and Use Committees (IACUC) govern the appro-
priate use of animals in research at each institution and must approve all animal
research procedures prior to initiation. The IACUC must include veterinarians, insti-
tutional scientists, nonscientists, and members of the public not otherwise associated
with the institution to provide a balanced view of the value of biomedical research
with the humane treatment of animals [1]. While specific guidelines for appropriate
use of animals in research are provided in the Guide for the Care and Use of
Laboratory Animals [1], these rules are interpreted by each IACUC for each instance,
leading to minor differences in experimental standards between institutions. Scientific
justification must also be supported by evidence that studies cannot be adequately
completed using nonanimal methods.
The goal of preclinical imaging with nanomaterials is to assess the biodistribu-
tion, pharmacokinetics, and toxicity of imaging agents in healthy animals and/or
disease models prior to translational studies and human clinical trials. Secondary
goals may include assessment of drug delivery and efficacy of therapeutic and diag-
nostic (theranostic) multifunctional nanomaterials or other biological effects not
directly related to imaging, but are not addressed here. To accomplish this goal,
nanomaterials are administered to animals, animals are anesthetized for imaging for
one or more sessions, and then the animals are euthanized to measure organ-specific
biodistribution. Minimal pain and distress occur for the animals, including anesthesia
and injections, qualifying these studies as Category C for pain and distress according
to the USDA Animal Welfare Act. Invasive imaging procedures that require deep
anesthesia and analgesics to manage pain would go under Category D . Classification
of pain and distress for model-specific procedures should be determined separately,
with advice from the local IACUC if needed.