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

Piotr Dzien; Ximena Raffo Iraolagoitia; Stephanie May; David Stevenson; Lynn McGarry; Dmitry Soloviev; Gavin Brown; Colin Nixon; Chrysa Kapeni; Maike De La Roche; Karen Blyth; Scott Lyons; Thomas Bird; Douglas Strathdee; Gilbert Fruhwirth; Leo Carlin; David Lewis

doi:10.21203/rs.3.rs-4196140/v1

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

Piotr Dzien, Ximena Raffo Iraolagoitia, Stephanie May, David Stevenson, Lynn McGarry, Dmitry Soloviev, Gavin Brown, Colin Nixon, Chrysa Kapeni, Maike De La Roche, Karen Blyth, Scott Lyons, Thomas Bird, Douglas Strathdee, Gilbert Fruhwirth, Leo Carlin, David Lewis

Comprehensive Cancer Centre

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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 (Rosa26 LSL - 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 Rosa26 LSL - 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.

Original language	English
Journal	Research square
DOIs	https://doi.org/10.21203/rs.3.rs-4196140/v1
Publication status	Published - 3 Apr 2024

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Dzien, P., Raffo Iraolagoitia, X., May, S., Stevenson, D., McGarry, L., Soloviev, D., Brown, G., Nixon, C., Kapeni, C., De La Roche, M., Blyth, K., Lyons, S., Bird, T., Strathdee, D., Fruhwirth, G., Carlin, L., & Lewis, D. (2024). Multi-scale in vivo imaging of tumour development using a germline conditional triple-reporter system. Research square. https://doi.org/10.21203/rs.3.rs-4196140/v1

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title = "Multi-scale in vivo imaging of tumour development using a germline conditional triple-reporter system",

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 (Rosa26 LSL - 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 Rosa26 LSL - 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. ",

author = "Piotr Dzien and {Raffo Iraolagoitia}, Ximena and Stephanie May and David Stevenson and Lynn McGarry and Dmitry Soloviev and Gavin Brown and Colin Nixon and Chrysa Kapeni and {De La Roche}, Maike and Karen Blyth and Scott Lyons and Thomas Bird and Douglas Strathdee and Gilbert Fruhwirth and Leo Carlin and David Lewis",

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doi = "10.21203/rs.3.rs-4196140/v1",

language = "English",

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Dzien, P, Raffo Iraolagoitia, X, May, S, Stevenson, D, McGarry, L, Soloviev, D, Brown, G, Nixon, C, Kapeni, C, De La Roche, M, Blyth, K, Lyons, S, Bird, T, Strathdee, D, Fruhwirth, G, Carlin, L & Lewis, D 2024, 'Multi-scale in vivo imaging of tumour development using a germline conditional triple-reporter system', Research square. https://doi.org/10.21203/rs.3.rs-4196140/v1

TY - JOUR

T1 - Multi-scale in vivo imaging of tumour development using a germline conditional triple-reporter system

AU - Dzien, Piotr

AU - Raffo Iraolagoitia, Ximena

AU - May, Stephanie

AU - Stevenson, David

AU - McGarry, Lynn

AU - Soloviev, Dmitry

AU - Brown, Gavin

AU - Nixon, Colin

AU - Kapeni, Chrysa

AU - De La Roche, Maike

AU - Blyth, Karen

AU - Lyons, Scott

AU - Bird, Thomas

AU - Strathdee, Douglas

AU - Fruhwirth, Gilbert

AU - Carlin, Leo

AU - Lewis, David

PY - 2024/4/3

Y1 - 2024/4/3

N2 - 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 (Rosa26 LSL - 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 Rosa26 LSL - 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.

AB - 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 (Rosa26 LSL - 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 Rosa26 LSL - 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.

U2 - 10.21203/rs.3.rs-4196140/v1

DO - 10.21203/rs.3.rs-4196140/v1

M3 - Article

C2 - 38645088

JO - Research square

JF - Research square

ER -

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

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