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Orthotopic Models with Advanced Imaging

Improve the predictive value of preclinical models with organ-specific TME and track disease progression in real time

Predictive Preclinical Benefits of Orthotopic Models

Orthotopic tumor models provide a clinically relevant, organ-specific tumor microenvironment (TME) to improve preclinical predictivity over subcutaneous alternatives. Generated by seeding tumor cells at the organ-specific site of the original tumor, orthotopic models mimic the primary lesion and establish better tumor, stroma, and immune component interactions than subcutaneous implantation.

This allows more human-disease relevant tumor development and progression, including spontaneous metastasis, recapitulating late-stage tumors. Orthotopic models therefore provide the ideal setting to:

  • investigate disease mechanisms
  • target the metastatic niche with new therapeutics
  • generate more patient-relevant response or resistance to anticancer agents.

Advances in Orthotopic Models

Orthotopic models offer many benefits but there remain challenges. Orthotopic implantation of cell lines can be time consuming, technically challenging and inefficient due to the laboratory and surgical procedures required to establish these tumor models. To address these challenges, Crown Bioscience has introduced high-frequency ultrasound to provide a less invasive and faster method of cell implantation, with significant improvements in animal welfare.

Learn More about high-frequency ultrasound

Ultrasound Imaging to Track Disease Progression and Metastasis

Unlike BLI, HF ultrasound imaging does not require the use of bioluminescently-tagged tumor models. This can reduce study lead time and eliminates the potential of loss-of signal due to necrotic tumor tissue in certain tumor types. Additionally, HF ultrasound offers 2D and 3D imaging for tumor tracking and precise measurement of tumor volume and location.

comparing CCl4 NASH induction in conventional and MS-NASH dysmetabolic models

Advantages of Imaging Orthotopic Models

 
  • Amenable to large scale studies and high throughput
  • Fast and efficient 2D and 3D imaging
  • Simplified positive randomization and optimal treatment initiation on established tumors across all groups
  • Cost effective platform - reducing animal number per study and providing more data from each animal

Our cutting edge imaging techniques and platforms include:

  • 2D bioluminescence, multispectral fluorescence, and spectral unmixing
  • 3D optical tomography (IVIS® Spectrum)
  • High-frequency ultrasound 2D and 3D in-life measurement of tumor volumes
  • Low dose and ultra-fast microCT (IVIS Spectrum/CT)
  • DyCE™ dynamic contrast enhanced imaging for real time distribution studies

Orthotopic Bioluminescent Models

 

Our panel of validated orthotopic bioluminescent models include syngeneic as well as xenograft lines.

  • Choose orthotopic bioluminescent models to monitor your compound antitumor activity in real time using bioluminescent imaging, in the presence of a relevant TME.

  • Choose bioluminescent experimental metastasis models to mimic hard to develop late-stage disease, such as bone or brain metastases, and obtain patient-relevant information on the metastatic niche. These models are established by seeding bioluminescent tumor cells either i.v. to facilitate lodging at the metastatic site, or directly into the organ where clinical metastases have been seen.

  • Choose bioluminescent systemic models for an easier monitoring of tumor burden and response to treatment in absence of palpable solid tumors via real time longitudinal imaging.



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