Multiscale in vivo imaging of tumor evolution using a germline conditional triple-reporter mouse

Area of Science:

• Oncology
• Molecular Imaging
• Genetics

Background:

• Imaging reporter genes are crucial for cancer research, enabling monitoring of tumor progression and treatment efficacy.
• Existing germline reporter models often utilize single imaging modalities with limited spatial resolution.
• There is a need for advanced reporter systems that offer multiscale and multimodal imaging capabilities for comprehensive biological studies.

Purpose of the Study:

• To develop an inducible triple-reporter mouse model integrating fluorescence, bioluminescence, and positron emission tomography (PET) for enhanced cancer research.
• To enable precise spatiotemporal control of reporter gene expression using inducible Cre-lox functionality.
• To facilitate multiscale, multimodal in vivo imaging for tracking biological processes from whole-body to cellular resolution.

Main Methods:

• Development of the inducible triple-reporter mouse model (Rosa26^LSL-NRL) incorporating reporters for fluorescence, bioluminescence, and PET.
• Utilizing inducible Cre-lox systems for spatiotemporal control of reporter gene expression in genetically engineered mouse models.
• Application of a multiscale, multimodal imaging approach, including bioluminescence, [¹⁸F]tetrafluoroborate PET/MRI, and in situ microscopy.

Main Results:

• Successful visualization of deep tissue oncogenesis in models of hepatocellular carcinoma and lung adenocarcinoma.
• Resolution of cell-cell interactions within tumor microenvironments using combined imaging modalities and microscopy.
• Demonstration of sensitive, tissue-specific, in vivo cell tracking across multiple spatial scales.

Conclusions:

• The developed triple-reporter system significantly advances in vivo cancer research capabilities.
• This model allows for comprehensive, multiscale investigation of biological processes within whole animals.
• The system facilitates sensitive and precise tracking of cells, aiding in the understanding of tumor evolution and microenvironment dynamics.