Development of a High-Throughput Molecular Imaging-Based Orthotopic Hepatocellular Carcinoma Model

Area of Science:

• Oncology
• Medical Imaging
• Small Animal Models

Background:

• Hepatocellular carcinoma (HCC) poses a significant global health challenge.
• Accurate early detection and monitoring of HCC progression are crucial for effective treatment.
• Existing small animal models may not fully recapitulate the complexities of human HCC.

Purpose of the Study:

• To develop and validate a novel orthotopic rat model for hepatocellular carcinoma (HCC).
• To assess the utility of bioluminescence imaging (BLI), positron emission tomography (PET), and ultrasound for early tumor detection and disease monitoring in this model.
• To establish a platform for high-throughput in vivo evaluation of image-guided therapies for HCC.

Main Methods:

• Developed a novel orthotopic rat HCC model by injecting HCC cells into the liver.
• Stably transfected HCC cells with a click beetle red reporter gene for BLI.
• Utilized serial BLI, PET, and ultrasound imaging at multiple time points (up to 28 days) to monitor tumor development and progression in vivo.
• Confirmed tumor implantation success rate (91.9%) and evaluated imaging modality sensitivity.

Main Results:

• Tumor formation was successfully established in 91.9% of the animals.
• Bioluminescence imaging (BLI) detected early tumor formation by Day 4, showing continuous growth.
• Positron emission tomography (PET) identified hypermetabolic activity by Days 14-15, with metastases detected after Day 24.
• Ultrasound visualized anatomical tumor growth starting around Days 10-12.
• BLI demonstrated the highest sensitivity for early tumor detection compared to PET and ultrasound.

Conclusions:

• A novel orthotopic rat HCC model has been successfully developed and validated.
• Molecular imaging techniques, particularly BLI, are highly effective for early detection and longitudinal monitoring of HCC in this model.
• This validated model provides a powerful tool for high-throughput in vivo assessment of image-guided therapies for hepatocellular carcinoma.