Animal Models

In vivo imaging of small laboratory animals (i.e., rats and mice) have emerged as a critical component of preclinical biomedical research. Small animal imaging provides a noninvasive means of assaying biological structure and function in vivo. Importantly, because of its noninvasive nature, imaging allows serial assay of small animal models of human cancer, neurological, cardiovascular and other diseases over the entire natural history of the disease process from inception to progression and monitoring of the effectiveness of treatment. The aim in preclinical molecular imaging studies is the investigation of the biodistribution of specific radiolabeled molecules in experimental animal models by modern dedicated small animal imaging devices, such as nanoScan PET/MRI or nanoScan SPECT/CT.

Animal models for preclinical cancer research

 

 

Syngeneic models

Syngeneic models include the spontaneous and the chemically induced tumors and in this case the inoculation of tumor cells in mice or rats genetically identical to those in which tumors were developed. Key Aplications:

Primer tumor and metastasis imaging: using 18F-FDG the metabolism of normal glucose can be monitored, and therefore even metastatic lesions are made visible

18F-FDG PET/MRI image of a subrenal transplanted syngenic tumor in a F344 rat model

Tumor angiogenesis imaging: using 68Ga-NOTA-c(NGR) as a specific ligand of the Aminopeptidase N (APN or CD13) that is revealed to be present in the new tumor vasculatures.

Tumor angiogenesis imaging: using 68Ga-NODAGA-(RGD) as a marker of integrin-expression. The integrins are are transmembrane receptors associated with receptor thyrosine kinases (RTKs) that play important role in the angiogenesis process.

Tumor prolifertion imaging: using 18F-FLT is an analog of the nucleoside thymidine, and a substrate of thymidine kinase I. The concentrtion of FLT nucleotides is proportional to thymidine kinase I activity, and therefore, imaging agent of cell proliferation.

 

 

 

 

 18F-FLT PET/MRI images of a highly proliferating tumor (right) and a slowly proliferationg tumor (left) in a mouse model

 

Xenogeneic models

Xenogeneic models include immune-compromised, immunodeficient animals transplanted with human cancers. 

Key Aplications:

Tumor metabolism imaging: tumor metabolism of human cancer transplanted to immunodefficient mice is monitored with 18F-FDG.


18
F-FDG PET/MRI image of human cancer transplanted xenograft mouse

 

Sites of transplantation

In both syngeneic and xenogeneic models, tumors can grow in heterotopic or orthotopic sites.

  • orthotopic transplantation: in this model the tumor xenograft is either implanted or injected into the equivalent organ from which the cancer originated
  • heterotopic transplantation: transfer of tissue from one part of a body of a donor to another area of the body of a recipient

- circulatory system (i.v., i.a., i.c.)
- specific tissues (s.c., i.d., i.m., organs
)

 

Animal models for preclinical brain research

 

Brain models
In the research field of brain studies it is necessary to use preclinical models to predict the effects of new pharmaceuticals. We provide small animal models and radiotracers for imaging of Alzheimer’s disease and tauopaties and Parkinson’s disease. Any further physiological conditions are also able to be investigated with all four tomography imaging modalities (PET/MRI and SPECT/CT).

Key Aplications:

Dopamine receptor imaging: 18F-Fallypride is a high affinity dopamine D2/D3 receptor antagonist, and therefore useful for imaging of the dopaminergic function, especially in the striatum

      

18F-Fallypride PET/MRI and single MRI images of a normal F344 rat model

Alzheimer's disease imaging: using 11C-PIB the amyloid neuritic plaques can be imaged, that are associated with Alzheimer's Disease (AD) and mild cognitive impairment (MCI).

 

 

Our References:

 

BBS NanoTech Ltd.

In cooperation with BBS NanoTech Ltd. the in vivo biodistribution of different  99mTc, 68Ga and 18F-labeled folate-targeted cancer nanosystems were investigated as new diagnostic agents in tumor-bearing mouse models using preclinical nanoScan SPECT/CT and PET/MRI imaging devices.

 

University of Szeged, Hungary

In cooperation with the University of Szeged (Aniko Keller-Pinter MD PhD, Department of Biochemistry, Faculty of Medicine) metabolic alterations in Compact mice were investigated by 18FDG-PET/MRI using congenic mice strain carrying wild-type myostatin and Compact genetic background.