Utilizing High Resolution Ultrasound to Monitor Tumor Onset and Growth in Genetically Engineered Pancreatic Cancer Models
April 7th, 2018
This article describes the utilization of high-resolution ultrasound in genetically engineered pancreatic cancer mice. The primary aim is to provide a detailed instruction for detection and evaluation of endogenous pancreatic tumors.
There are various genetically engineered mouse models to study pancreatic cancer. The most commonly used model is the Kras, p53 mouse model that harbors an activating mutation in the Kras oncogene, and an inactivating mutation in the p53 tumor suppressor gene. Both mutations are conditionally activated by the Pdx-Cre promoter.
This Kras, p53, Pdx-Cre mouse model, in short KPC model, develops endogenous pancreatic tumors between the age of two to six month. In preparation of your ultrasound procedure, the following equipment should be prepared and ready to use. For high resolution ultrasound, a stationary ultrasound device is used.
The ultrasound procedure is conducted in general anesthesia using isoflurane evaporation. Once the mouse is under deep sedation, it is transferred to the green working stage. After the ultrasound procedure, the mouse should be placed in a pre-heated cage to accelerate recovery.
Tumor development is highly variable in the KPC mouse model. To avoid unnecessary ultrasound screening procedures, we usually perform abdominal palpation weekly starting from the age of two months. Gently, palpate the mouse abdomen up and down to detect any pancreatic tumors.
Keep in mind that hard feces may mimic abdominal tumor masses. After initiation of general anesthesia, in a separate induction chamber, the mouse is carefully placed onto the green and pre-heated working stage. During the ultrasound procedure, isoflurane is continuously supplied via the nose cone.
Fix the trandsucer head at the top of your working stage by using the mounting system. Perform the foot-pinch test to make sure the mouse is under deep anesthesia. Afterwards, the mouse is fixed onto the working platform using medical strips.
It is crucial to completely remove the abdominal fur prior to the ultrasound procedure, to avoid any artifacts. First, carefully shave off the mouse fur. Great care should be taken to avoid any superficial skin lacerations using the pet clipper.
Second, apply a thin layer of the depilatory cream onto the shaved area. Completely remove the cream using moist tissues. Apply abundant ultrasound gel onto the mouse abdomen, and a thin layer of gel directly onto the ultrasound probe.
Adjust the transducer onto the abdomen using soft pressure. Heavy compression of the mouse abdomen may lead to respiratory or circulatory impairment, and should be avoided. Scan up and down and adjust the frame of the working platform and the wheels for the x and y axis.
Some tumors may only be visible by changing the initial position of the mouse. To correctly interpret B-mode ultrasound images, basic anatomical knowledge is required. In the KPC mouse model, pancreatic tumors can be detected in the head, body, or tail of the pancreas.
The tumors usually demarcate as hypoechoic masses. Due to their desmoplastic features, these tumors are usually hard to compress by the ultrasound probe. Following the ultrasound, completely remove the ultrasound gel and gently place the mouse in the pre-heated recovery cage.
Once you identified a tumor, scan up and down to get an impression of the total size, and measure the largest diameter by using the ultrasound caliper. For the exact volume calculation, we use the formula of an ellipsoid. After finishing the measurement of the first plane, either rotate the scan-head by 90 degree, in a longitudinal position, or turn the mouse to its side, to detect the tumor's longitudinal expansion.
For the evaluation of novel therapeutic approaches, it is important to determine the initial tumor volume and the tumor growth kinetics during treatment. During pre-clinical trials, abdominal ultrasound can be repeated every three to four days to monitor tumor growth.
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Overview
This article describes the utilization of high-resolution ultrasound in genetically engineered pancreatic cancer mice. The primary aim is to provide a detailed instruction for detection and evaluation of endogenous pancreatic tumors.
Key Study Components
Area of Science
- Neuroscience
- Oncology
- Imaging Techniques
Background
- Genetically engineered mouse models are essential for studying pancreatic cancer.
- The Kras, p53 mouse model is commonly used for this purpose.
- This model develops endogenous pancreatic tumors between two to six months of age.
- Ultrasound is a key technique for evaluating these tumors.
Purpose of Study
- To provide a detailed protocol for using high-resolution ultrasound.
- To facilitate the detection of pancreatic tumors in mouse models.
- To enhance the evaluation of tumor characteristics.
Methods Used
- Preparation of a stationary ultrasound device.
- Utilization of the Kras, p53, Pdx-Cre mouse model.
- Conducting high-resolution ultrasound procedures.
- Evaluation of endogenous pancreatic tumors.
Main Results
- Successful detection of pancreatic tumors using ultrasound.
- Detailed imaging of tumor characteristics.
- Validation of the ultrasound technique in a mouse model.
- Insights into the progression of pancreatic cancer.
Conclusions
- High-resolution ultrasound is effective for tumor evaluation.
- The KPC model is a valuable tool for pancreatic cancer research.
- This method can improve understanding of tumor biology.
Frequently Asked Questions
Executive Industry Relevance
High-resolution ultrasound enables non-invasive, quantitative monitoring of tumor onset and progression in genetically engineered pancreatic cancer models, addressing the challenge of variable tumor development timelines. This imaging capability supports robust preclinical evaluation of therapeutic candidates by providing real-time, longitudinal data on tumor kinetics. Integrating such imaging tools enhances predictive confidence and informs critical go/no-go decisions in oncology drug discovery pipelines.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Enables precise detection and measurement of endogenous tumor formation in disease-relevant models.
- Supports functional validation of genetic drivers and therapeutic targets in vivo.
- Facilitates mechanistic de-risking by correlating genetic alterations with tumor phenotypes.
- Improves predictive confidence for target engagement and pathway modulation studies.
Screening & Assay Development
- Provides standardized, reproducible imaging outputs for quantitative tumor burden assessment.
- Enables repeated, non-terminal measurements to monitor treatment response over time.
- Supports assay development for evaluating efficacy of novel compounds in vivo.
- Reduces animal usage by allowing longitudinal studies within the same cohort.
Translational & Preclinical Research
- Aligns preclinical tumor growth kinetics with clinical disease progression for translational relevance.
- Enables risk-adjusted advancement of candidates based on real-time efficacy data.
- Supports biomarker discovery by correlating imaging findings with molecular endpoints.
- Facilitates continuity from early discovery through preclinical validation in oncology portfolios.
Pipeline & Workflow Integration
High-resolution ultrasound integrates into the preclinical discovery continuum, bridging early target validation, lead identification, and translational research in oncology models.
- Discovery Biology: Provides in vivo evidence for hypothesis testing and pathway interrogation in genetically engineered models.
- Screening: Delivers reproducible, quantitative tumor measurements to support compound screening and efficacy ranking.
- Analytics: Enables statistical comparison of tumor growth rates and treatment responses across experimental arms.
- Translational Research: Aligns preclinical imaging endpoints with clinical trial metrics for improved translational continuity.
- Enterprise Reuse: Establishes a reusable imaging platform applicable across multiple oncology programs and genetic models.
Operational & Enterprise Impact
- Scientific Value: Enhances predictive confidence and reduces mechanistic ambiguity in tumor biology studies.
- Operational Value: Standardizes imaging protocols for reproducibility and scalability across studies.
- Strategic Value: Informs go/no-go decisions and optimizes resource allocation by providing early efficacy readouts.
- Portfolio Impact: Supports risk-adjusted prioritization and advancement of oncology assets based on robust preclinical data.
Implementation Considerations
- Requires expertise in murine anatomy and high-resolution ultrasound operation.
- Demands access to specialized imaging instrumentation and analytical software.
- Necessitates cross-team standardization of imaging protocols and measurement criteria.
- May require adaptation for different tumor locations or genetic backgrounds in mouse models.
- Operator skill and anatomical knowledge are critical to avoid artifacts and ensure data quality.
