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

Raffo-Iraolagoitia, Ximena L, Alyamani, Abdullah, May, Stephanie, Stevenson, David, Mackintosh, Agata, McGarry, Lynn, Anand, Jayanthi, Soloviev, Dmitry, Brown, Gavin, Nixon, Colin, Kapeni, Chrysa, De La Roche, Maike, Blyth, Karen, Bird, Thomas Graham, Strathdee, Douglas, Lyons, Scott K, Fruhwirth, Gilbert, Carlin, Leo M, Lewis, David Y (July 2026) Multiscale in vivo imaging of tumor evolution using a germline conditional triple-reporter mouse. Nature Biotechnology. ISSN 1087-0156

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Abstract

Imaging reporter genes are essential tools in cancer research for monitoring tumor evolution, cell dissemination, gene activation and treatment response. However, germline reporter models typically rely on single imaging modalities operating over limited spatial scales. To address these limitations, we developed an inducible triple-reporter mouse model (Rosa26LSL-NRL) that integrates three reporters for complementary imaging modalities, fluorescence, bioluminescence and positron emission tomography (PET), along with inducible Cre-lox functionality for precise spatiotemporal control of reporter expression in genetically engineered mouse models. Using a multiscale, multimodal approach, we visualize deep tissue oncogenesis in models of hepatocellular carcinoma and lung adenocarcinoma and, guided by whole-body imaging with bioluminescence and [18F]tetrafluoroborate PET/magnetic resonance imaging (MRI), resolve cell-cell interactions within tumor microenvironments using in situ microscopy. This triple-reporter system enables multiscale investigation of biological processes within whole animals, facilitating sensitive, tissue-specific, in vivo cell tracking from whole-body to cellular resolution.

Item Type:	Paper
Subjects:	diseases & disorders > cancer diseases & disorders organism description > animal organism description > animal > mammal organism description > animal > mammal > rodent > mouse organism description > animal > mammal > rodent
CSHL Authors:	Lyons, Scott
Communities:	CSHL labs > Lyons lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	15 July 2026
Date Deposited:	17 Aug 2026 12:42
Last Modified:	17 Aug 2026 12:42
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/42292

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