Near-Infrared Bioluminescence Imaging of Macrophage Sensors for Cancer Detection In Vivo

Giorgia Zambito; Gunja Mishra; Christopher Schliehe; Laura Mezzanotte

doi:10.3389/fbioe.2022.867164

Near-Infrared Bioluminescence Imaging of Macrophage Sensors for Cancer Detection In Vivo

Giorgia Zambito
, Gunja Mishra
, Christopher Schliehe
, Laura Mezzanotte^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

12 Citations (Scopus)

98 Downloads (Pure)

Abstract

Melanoma is an aggressive type of skin cancer with a poor prognosis after it gets metastasized. The early detection of malignant melanoma is critical for effective therapy. Because melanoma often resembles moles, routine skin check-up may help for timely identification of suspicious areas. Recently, it has been shown that the interplay of melanoma cells with the immune system can help develop efficient therapeutic strategies. Here, we leveraged engineered macrophages (BMC2) as cell-based sensors for metastatic melanoma. To perform dual-color bioluminescence imaging (BLI) in vivo, macrophages were engineered to express a green click beetle luciferase (CBG2) and a near-infrared fluorescent dye (DiR), and B16F10 melanoma cells were instead engineered to express a near-infrared click beetle luciferase (CBR2). Using real-time in vivo dual-color BLI and near-infrared fluorescence (FL) imaging, we could demonstrate that macrophages were able to sense and substantially accumulate in subcutaneous and metastatic melanoma tissues at 72 h after systemic injections. Together, we showed the potentiality to use optical imaging technologies to track circulating macrophages for the non-invasive detection of metastatic melanoma.

Original language	English
Article number	867164
Journal	Frontiers in Bioengineering and Biotechnology
Volume	10
DOIs	https://doi.org/10.3389/fbioe.2022.867164
Publication status	Published - 9 May 2022

Bibliographical note

Funding Information:
We acknowledge the funding for this project by the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 777682. GM was supported by the LEaDing Postdoc Fellowship Program, a Horizon 2020 Marie Sklodowska-Curie COFUND. This work was supported by the Applied Molecular Imaging Erasmus MC (AMIE) facility. We thank Mary Hall, Lance Encell, Thomas Kirkland, and Ce Shi from Promega for the fruitful discussion and synthesis of naphthyl luciferin.

Publisher Copyright: Copyright © 2022 Zambito, Mishra, Schliehe and Mezzanotte.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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Cite this

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title = "Near-Infrared Bioluminescence Imaging of Macrophage Sensors for Cancer Detection In Vivo",

abstract = "Melanoma is an aggressive type of skin cancer with a poor prognosis after it gets metastasized. The early detection of malignant melanoma is critical for effective therapy. Because melanoma often resembles moles, routine skin check-up may help for timely identification of suspicious areas. Recently, it has been shown that the interplay of melanoma cells with the immune system can help develop efficient therapeutic strategies. Here, we leveraged engineered macrophages (BMC2) as cell-based sensors for metastatic melanoma. To perform dual-color bioluminescence imaging (BLI) in vivo, macrophages were engineered to express a green click beetle luciferase (CBG2) and a near-infrared fluorescent dye (DiR), and B16F10 melanoma cells were instead engineered to express a near-infrared click beetle luciferase (CBR2). Using real-time in vivo dual-color BLI and near-infrared fluorescence (FL) imaging, we could demonstrate that macrophages were able to sense and substantially accumulate in subcutaneous and metastatic melanoma tissues at 72 h after systemic injections. Together, we showed the potentiality to use optical imaging technologies to track circulating macrophages for the non-invasive detection of metastatic melanoma.",

author = "Giorgia Zambito and Gunja Mishra and Christopher Schliehe and Laura Mezzanotte",

note = "Funding Information: We acknowledge the funding for this project by the European Union{\textquoteright}s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 777682. GM was supported by the LEaDing Postdoc Fellowship Program, a Horizon 2020 Marie Sklodowska-Curie COFUND. This work was supported by the Applied Molecular Imaging Erasmus MC (AMIE) facility. We thank Mary Hall, Lance Encell, Thomas Kirkland, and Ce Shi from Promega for the fruitful discussion and synthesis of naphthyl luciferin. Publisher Copyright: Copyright {\textcopyright} 2022 Zambito, Mishra, Schliehe and Mezzanotte.",

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N2 - Melanoma is an aggressive type of skin cancer with a poor prognosis after it gets metastasized. The early detection of malignant melanoma is critical for effective therapy. Because melanoma often resembles moles, routine skin check-up may help for timely identification of suspicious areas. Recently, it has been shown that the interplay of melanoma cells with the immune system can help develop efficient therapeutic strategies. Here, we leveraged engineered macrophages (BMC2) as cell-based sensors for metastatic melanoma. To perform dual-color bioluminescence imaging (BLI) in vivo, macrophages were engineered to express a green click beetle luciferase (CBG2) and a near-infrared fluorescent dye (DiR), and B16F10 melanoma cells were instead engineered to express a near-infrared click beetle luciferase (CBR2). Using real-time in vivo dual-color BLI and near-infrared fluorescence (FL) imaging, we could demonstrate that macrophages were able to sense and substantially accumulate in subcutaneous and metastatic melanoma tissues at 72 h after systemic injections. Together, we showed the potentiality to use optical imaging technologies to track circulating macrophages for the non-invasive detection of metastatic melanoma.

AB - Melanoma is an aggressive type of skin cancer with a poor prognosis after it gets metastasized. The early detection of malignant melanoma is critical for effective therapy. Because melanoma often resembles moles, routine skin check-up may help for timely identification of suspicious areas. Recently, it has been shown that the interplay of melanoma cells with the immune system can help develop efficient therapeutic strategies. Here, we leveraged engineered macrophages (BMC2) as cell-based sensors for metastatic melanoma. To perform dual-color bioluminescence imaging (BLI) in vivo, macrophages were engineered to express a green click beetle luciferase (CBG2) and a near-infrared fluorescent dye (DiR), and B16F10 melanoma cells were instead engineered to express a near-infrared click beetle luciferase (CBR2). Using real-time in vivo dual-color BLI and near-infrared fluorescence (FL) imaging, we could demonstrate that macrophages were able to sense and substantially accumulate in subcutaneous and metastatic melanoma tissues at 72 h after systemic injections. Together, we showed the potentiality to use optical imaging technologies to track circulating macrophages for the non-invasive detection of metastatic melanoma.

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Near-Infrared Bioluminescence Imaging of Macrophage Sensors for Cancer Detection In Vivo

Abstract

Bibliographical note

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