Traditional anti-cancer studies
Assessment of anti-cancer activity by caliper measurements of subcutaneous tumors remains the most often requested method for cancer drug evaluation at MIR Preclinical Services. These studies involve injecting an animal with a subcutaneous tumor and monitoring tumor progression in groups treated with compound versus that of control groups. However, this method is not applicable to most orthotopic or transgenic systems that are becoming increasingly popular. In addition, this method does not yield information about blood flow, vascularity, angiogenesis, tumor metabolism, edema and other factors that can be ascertained with non-invasive imaging.

T₂ weighted MRI

• Rapid and relatively inexpensive. Does not require a contrast agent for image
  

• Difficult to distinguish between edema and tumor tissue in certain orthotopic tumors

T₁ weighted MRI

• Can be used with gadolinium based contrast agents to obtain increased contrast between different tissue types. For example, delineation of tumor and normal tissue or edema

• Generally requires contrast agent injection which increases preparation times and adds complexity

Use of T₁ and T₂ weighted MRIs

• Can distinguish and quantify tumor and edema volume
  

• Requires two separate images and contrast agent injection

• Detection and growth determination of orthotopic tumors and metastases possible

• Assessment of viable fraction for characterization of cytostatic treatment effectiveness

• High throughput imaging of multiple mice simultaneously in less than a minute
  

• A luciferase expressing tumor cell line is required

• Requires systemic luciferin injection

• Tumor cell lines expressing a fluorescent label enable imaging of orthotopic tumors and metastases

• Multiple fluorescent tags of differing inherent wavelengths may be used to assess tumor burden and other functional endpoints in a single study

• High throughput imaging of multiple mice simultaneously in less than a minute
  Requires no substrate injection
  

• High background fluorescence presents quantitation challenges

• Requires a fluorescent labeled tumor cell line

Assessment of tumor burden in bone- µCT

ADVANTAGES

LIMITATIONS

• Detection of bone metastases
  

• Requires the use of a continuous intravenous contrast agent injection

MRI

Bioluminescence

Fluorescence

µPET

• Quantitative metabolic imaging of 18F- Fluorodeoxyglucose and other positron emitting compounds for tumor detection, assessment of metabolism, tissue perfusion, receptor binding and other applications

• Well accepted translational modality

• Relatively low spatial resolution, requires injection of radiolabeled material

• Short lived isotopes may limit experimental design

Spectroscopic MRI

• Quantitative and spatially resolved assessment of a variety of metabolites, including ATP, Phosphocreatine, choline, N-acetyl-aspartate and lactate

• Generally requires a compromise between spacial resolution and sensitivity

• Generally low throughput

µCT

• High spatial resolution for anatomical imaging of ex-vivo tissue

• In vivo assessment of soft tissue and skeletal microstructure

• Acquisition of isotropic 3-dimensional data allows sophisticated data analysis such as 3D surface and volume rendering

• For in vivo subjects, exposure to ionizing radiation can limit the frequency of repeated scans

• Use of CT contrast agents may be necessary in order to obtain soft tissue image contrast

MRI

• Flexibility with choice of contrast (T1, T2, T2*, T1-rho, diffusion, etc.)

• Completely non-invasive

• Acquisition of 3-dimensional data allows sophisticated data analysis such as 3D surface and volume rendering

• Typically lower resolution for in vivo imaging

• Relatively long image times required for high resolution ex vivo imaging

µCT

• High resolution three dimensional in-vivo anatomical imaging

• Especially useful for skeletal imaging

• assessment of body composition (eg. fat content)

• Acquisition of 3-dimensional data allows sophisticated data analysis such as 3D surface and volume rendering

• Exposure to ionizing radiation can limit the frequency of repeated scans

MRI

• High flexibility with choice of tissue contrast (T₁, T₂, T₂*, T₁-rho,
  diffusion etc.)

• Completely non-invasive

• Can be relatively high throughput, depending on the required readout (5 minutes per animal possible)

• Acquisition of 3-dimensional data allows sophisticated data analysis such as 3D surface and volume rendering

• Relatively long image times required for highest resolution 3-dimensional scanning

MRI

• In vivo localized spectroscopy of 2D and 3D voxel arrays for chemical shift analysis (CSA) allows non-invasive quantification of small molecule tissue concentration

• Relatively low throughput

• Relatively low sensitivity, requires micro-molar concentrations

• Can be difficult or impossible due to high background of the detected molecules

PET

• Can be both highly sensitive and highly specific

• Requires specialized chemistry to generate the appropriate radiolabeled molecule

MRI

• Flexibility with choice of contrast (T₁, T₂, T₂*, T₁-rho, diffusion, etc.)

• Completely non-invasive

• Physiological measures may not probe target modulation or molecular level events

Traditional Biochemical and Histological Methods

• MIR can prepare tissue samples from treated animals for analysis in client laboratories. Fixed tissues, frozen tumor slices, and snap frozen tumor powders are suitable for a variety of conventional analytical techniques including immunohistochemistry, western blots, and RNA expression profiling

• MIR can apply the above techniques to your samples

• Animals have to be sacrificed in order to obtain samples for analysis

• For multiple time points within a study, large cohorts of animals have to be used because the procedure is invasive