# Multi-scale in vivo imaging of tumour development using a germline conditional triple-reporter system

## TL;DR

This paper introduces a new mouse model that allows multi-scale imaging of tumor development using three complementary imaging techniques.

## Contribution

The novel contribution is an inducible triple-reporter mouse system combining fluorescence, bioluminescence, and PET for multi-scale tumor imaging.

## Key findings

- The triple-reporter system enables robust and inducible imaging across multiple tissues.
- It allows precise tumor localization and visualization of cell-cell interactions in the tumor microenvironment.
- The system supports multi-scale investigation from whole-body to cellular levels.

## Abstract

Imaging reporter genes are indispensable for visualising biological processes in living subjects, particularly in cancer research where they have been used to observe tumour development, cancer cell dissemination, and treatment response. Engineering reporter genes into the germline frequently involves single imaging modality reporters operating over limited spatial scales. To address these limitations, we developed an inducible triple-reporter mouse model (Rosa26LSL – NRL) that integrates reporters for complementary imaging modalities, flfluorescence, bioluminescence and positron emission tomography (PET), along with inducible Cre-lox functionality for precise spatiotemporal control of reporter expression. We demonstrated robust reporter inducibility across various tissues in the Rosa26LSL – NRL mouse, facilitating effective tracking and characterisation of tumours in liver and lung cancer mouse models. We precisely pinpointed tumour location using multimodal whole-body imaging which guided in situ lung microscopy to visualise cell-cell interactions within the tumour microenvironment. The triple-reporter system establishes a robust new platform technology for multi-scale investigation of biological processes within whole animals, enabling tissue-specific and sensitive cell tracking, spanning from the whole-body to cellular scales.