Animal Models for Preclinical Imaging - Nanotechnology for Biomedical Imaging and Diagnostics - page 458

16.3 considerAtions in AnimAl cAre

Proper maintenance of animal health and welfare is also necessary for producing
reliable experimental results. Inadequate care can adversely affect imaging results
due to infection, inflammation, and alterations of blood flow.

16.3.1 drug formulation

Current regulations on animal use in research compel investigators to use pharmaceu-
tical grade materials (FDA approved) in all animal studies, including acute, nonsurvival
studies when available [1]. Scientific justification is needed for use of unapproved
agents, which include almost all nanomaterials. The local IACUC may require evalua-
tion of grade, purity, sterility, pyrogenicity, stability, and other factors prior to approval
for use in animal studies. While the primary aim of these regulations is animal safety,
these factors are also important for the validity of experimental results and conclusions.
Investigators are therefore encouraged to evaluate these factors for each formulation
prior to conducting animal studies.
Synthesis of nanomaterial imaging agents is performed in a chemical laboratory,
often utilizing organic solvents and nonbiocompatible constituents. Nanomaterials
must be transitioned to biocompatible, pharmaceutical grade formulations prior to
administration. In general, nanomaterials should be formulated in sterile, pH-buffered
aqueous solution such as PBS for intravenous injection. Analysis of nanomaterials in
the final formulation should be performed to ensure that the desired characteristics are
maintained, including solubility and stability. For example, gold nanoparticles (NPs)
were 50 nm in diameter in ultrapure water but increased to 200-250 nm when dispersed in
PBS [2]. Aggregation of NPs will significantly alter the pharmacokinetics and biodistribu-
tion relative to well-dispersed solutions and adversely affect experimental conclusions.

16.3.2 dose calculations

The dose of material administered to laboratory animals for imaging studies should be
based on several factors. Animals vary significantly in size (Fig. 16.1) as determined
by body weight (BW), body surface area (BSA), or body mass index (BMI) [3, 4].
Metabolic rates also increase with decreasing size, which affects pharmacokinetics and
organ-specific uptake rates. The administered dose is of particular concern for molec-
ular imaging using contrast agents that target saturable receptors or enzymes. Doses
close to or above that required for saturation of the relevant binding sites can adversely
affect conclusions from an imaging study by reducing the target-specific uptake and
contrast [4]. Mass effect must be considered when choosing a dose for molecular
imaging alongside detection sensitivity and resolution of the imaging modality used.

16.3.3 Anesthesia

Imaging of animals is generally performed under heavy sedation or full anesthesia.
Anesthesia can be delivered by systemic injection (e.g., ketamine/xylazine) or by
inhalation (e.g., isoflurane). Injectable anesthesia is beneficial for procedures less