PET Imaging Studies
Positron emission tomography (PET) imaging is a valuable tool in neuroscience and oncology research studies to measure brain functionality and metabolism and is increasingly being used as a preclinical endpoint to predict clinical success. Increasingly, PET is also used to monitor metabolic activity in brain tumors. PET imaging can be performed with CT to get combined data on radioligand accumulation and anatomic localization. Additionally, PET imaging using custom PET tracers can also be combined with SPECT imaging that employs gamma ray emitting isotopes.
Charles River’s expertise with small animal imaging and associated ex vivo techniques, provide a comprehensive state-of-the-art toolkit to evaluate the pathophysiology and drug effects in animal models of neurological disease. Access to a cyclotron in close vicinity is used to produce short-lived positron-emitting isotopes suitable for PET imaging. In addition, arterial input function (AIF) can be generated to quantify target area concentration that is normalized to cumulative arterial radioligand concentration from the time of injection until the end of the scan.
PET tracers such as 18F-FDG are used to perform preclinical PET imaging. Different PET tracers are used for various study types - for example, radiolabeled FDG is used to study brain metabolism, neuroinflammation is measured using radioactively labeled TSPO PET ligand. Diverse and customizable PET tracers are available at Charles River to investigate various cellular events including GPCR activation, receptor occupancy, brain perfusion etc. PET imaging is widely used to study neuroinflammation, glucose metabolism and other physiological processes in various neurological disorders including Alzheimer’s disease and Parkinson’s disease.
We validate targets, study drug candidates, and develop custom PET ligands. Noninvasive testing methods like PET imaging are easily combined with behavioral and biochemical readouts to provide translational preclinical data to support more optimally designed clinical trials that include PET imaging as a readout.
Figure 1: Imaging of reduction of dopamine transporter (DAT) levels in the MPTP model of Parkinson’s disease using the PET ligand 18F-FE-PE2I
Figure 2: Chart data of reduction of dopamine transporter (DAT) levels in the MPTP model of Parkinson’s disease using the PET ligand 18F-FE-PE2I
PET Imaging FAQs
Can imaging be performed along with other tests in the same animal?
Yes. The advantage of nuclear imaging is that it can be combined with other studies such as behavioral studies, histology and anatomical image MRIs.
When biochemical analyses are performed on postmortem samples from animals injected with radioactive tracers, are these analyses conducted in a lab certified for isotope work or are the samples stored in quarantine until the isotope decays?
It depends on the half-life of the isotope. It is possible to store samples that have shorter half-life isotopes before performing additional analyses but in cases where the isotope half-life is very long (such as 14C), the sample will need to be analyzed in a lab certified for isotope work.
Can the distribution of supramolecular structures (e.g., liposomes, nanoparticles) be imaged?
Yes. We have done nanoparticle distribution studies and plan to increase our capabilities in imaging supramolecular structures.
Does Charles River offer receptor occupancy studies and how do these studies compare with PET imaging data?
We offer receptor occupancy studies using H-3 labeled compounds but we do not have comparison data between H-3 studies and PET imaging at this time. The availability of the ligands has not yet supported this work.
For the 18F-TSPO ligand, is autoradiography preferred over PET imaging for the EAE, cuprizone and LPS models?
It depends on the data that needs to be generated. If the imaging needs to be done more slowly over a longer time period, then autoradiography is preferable as it has a larger time window. PET imaging is preferable for more sensitive data output.
Does Charles River have access to a cyclotron? Can custom radiolabeling of molecules with F-18, radioiodines and radiometals be performed?
Charles River has access to a local cyclotron and we have an agreement in place to synthesize custom ligands and perform radiolabeling. Current radiolabeling capabilities include fluoride-18, carbon-11 and gallium-68 PET ligand nuclides. Iodine-125 labeling is also possible.
Does Charles River have the ability to measure in vivo bioluminescence using reporter mice?
Yes. We can measure bioluminescence at the Charles River Finland site. Please email [email protected] to get more information.
What is a typical sample size for efficacy studies using PET/SPECT imaging?
Reference efficacy studies can be performed with a group of 5 animals. For a novel compound study using PET imaging, the recommended sample size is at least 10 animals for statistically significant data.
Has Charles River used imaging to quantify amyloid plaques in models of Alzheimer’s disease?
Yes. We have ongoing studies to quantify amyloid plaques in mouse models of Alzheimer’s disease.
Do you have the hardware and skills for multi-spectral optoacoustic tomography for use with fluorescent probes?
At this time, we do not have optoacoustic imaging capabilities in house and it is important to note that this imaging modality has major challenges - limited depth of light penetrance in brain tissues and the barrier presented by the skull. However, we do have collaborations in place to perform imaging using fluorescent probes.