Novel theranostic agent for PET imaging and targeted radiopharmaceutical therapy of tumour-infiltrating immune cells in glioma
Abstract
Background: Malignant gliomas are deadly tumours with few therapeutic options. Although immunotherapy may be a promising therapeutic strategy for treating gliomas, a significant barrier is the CD11b+ tumour-associated myeloid cells (TAMCs), a heterogeneous glioma infiltrate comprising up to 40% of a glioma's cellular mass that inhibits anti-tumour T-cell function and promotes tumour progression. A theranostic approach uses a single molecule for targeted radiopharmaceutical therapy (TRT) and diagnostic imaging; however, there are few reports of theranostics targeting the tumour microenvironment. Methods: Utilizing a newly developed bifunctional chelator, Lumi804, an anti-CD11b antibody (αCD11b) was readily labelled with either Zr-89 or Lu-177, yielding functional radiolabelled conjugates for PET, SPECT, and TRT. Findings: 89Zr/177Lu-labeled Lumi804-αCD11b enabled non-invasive imaging of TAMCs in murine gliomas. Additionally, 177Lu-Lumi804-αCD11b treatment reduced TAMC populations in the spleen and tumour and improved the efficacy of checkpoint immunotherapy. Interpretation: 89Zr- and 177Lu-labeled Lumi804-αCD11b may be a promising theranostic pair for monitoring and reducing TAMCs in gliomas to improve immunotherapy responses.
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- Univ. of Pittsburgh, PA (United States)
- Lumiphore, Inc., Berkeley, CA (United States)
- Univ. of Missouri, Columbia, MO (United States)
- Univ. of Pittsburgh, PA (United States); Univ. of Missouri, Columbia, MO (United States)
- Publication Date:
- Research Org.:
- Univ. of Pittsburgh, PA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Nuclear Physics (NP); UPMC Hillman Cancer Center
- OSTI Identifier:
- 1904053
- Grant/Contract Number:
- P30 CA047904
- Resource Type:
- Accepted Manuscript
- Journal Name:
- EBioMedicine
- Additional Journal Information:
- Journal Volume: 71; Journal Issue: C; Journal ID: ISSN 2352-3964
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; theranostics; targeted radiotherapy; immunoPET; checkpoint immunotherapy; gliomas; bifunctional chelator
Citation Formats
Foster, Alexandra, Nigam, Shubhanchi, Tatum, David S., Raphael, Itay, Xu, Jide, Kumar, Rajeev, Plakseychuk, Elizabeth, Latoche, Joseph D., Vincze, Sarah, Li, Bo, Giri, Rajan, McCarl, Lauren H., Edinger, Robert, Ak, Murat, Peddagangireddy, Vishal, Foley, Lesley M., Hitchens, T. Kevin, Colen, Rivka R., Pollack, Ian F., Panigrahy, Ashok, Magda, Darren, Anderson, Carolyn J., Edwards, W. Barry, and Kohanbash, Gary. Novel theranostic agent for PET imaging and targeted radiopharmaceutical therapy of tumour-infiltrating immune cells in glioma. United States: N. p., 2021.
Web. doi:10.1016/j.ebiom.2021.103571.
Foster, Alexandra, Nigam, Shubhanchi, Tatum, David S., Raphael, Itay, Xu, Jide, Kumar, Rajeev, Plakseychuk, Elizabeth, Latoche, Joseph D., Vincze, Sarah, Li, Bo, Giri, Rajan, McCarl, Lauren H., Edinger, Robert, Ak, Murat, Peddagangireddy, Vishal, Foley, Lesley M., Hitchens, T. Kevin, Colen, Rivka R., Pollack, Ian F., Panigrahy, Ashok, Magda, Darren, Anderson, Carolyn J., Edwards, W. Barry, & Kohanbash, Gary. Novel theranostic agent for PET imaging and targeted radiopharmaceutical therapy of tumour-infiltrating immune cells in glioma. United States. https://doi.org/10.1016/j.ebiom.2021.103571
Foster, Alexandra, Nigam, Shubhanchi, Tatum, David S., Raphael, Itay, Xu, Jide, Kumar, Rajeev, Plakseychuk, Elizabeth, Latoche, Joseph D., Vincze, Sarah, Li, Bo, Giri, Rajan, McCarl, Lauren H., Edinger, Robert, Ak, Murat, Peddagangireddy, Vishal, Foley, Lesley M., Hitchens, T. Kevin, Colen, Rivka R., Pollack, Ian F., Panigrahy, Ashok, Magda, Darren, Anderson, Carolyn J., Edwards, W. Barry, and Kohanbash, Gary. Mon .
"Novel theranostic agent for PET imaging and targeted radiopharmaceutical therapy of tumour-infiltrating immune cells in glioma". United States. https://doi.org/10.1016/j.ebiom.2021.103571. https://www.osti.gov/servlets/purl/1904053.
@article{osti_1904053,
title = {Novel theranostic agent for PET imaging and targeted radiopharmaceutical therapy of tumour-infiltrating immune cells in glioma},
author = {Foster, Alexandra and Nigam, Shubhanchi and Tatum, David S. and Raphael, Itay and Xu, Jide and Kumar, Rajeev and Plakseychuk, Elizabeth and Latoche, Joseph D. and Vincze, Sarah and Li, Bo and Giri, Rajan and McCarl, Lauren H. and Edinger, Robert and Ak, Murat and Peddagangireddy, Vishal and Foley, Lesley M. and Hitchens, T. Kevin and Colen, Rivka R. and Pollack, Ian F. and Panigrahy, Ashok and Magda, Darren and Anderson, Carolyn J. and Edwards, W. Barry and Kohanbash, Gary},
abstractNote = {Background: Malignant gliomas are deadly tumours with few therapeutic options. Although immunotherapy may be a promising therapeutic strategy for treating gliomas, a significant barrier is the CD11b+ tumour-associated myeloid cells (TAMCs), a heterogeneous glioma infiltrate comprising up to 40% of a glioma's cellular mass that inhibits anti-tumour T-cell function and promotes tumour progression. A theranostic approach uses a single molecule for targeted radiopharmaceutical therapy (TRT) and diagnostic imaging; however, there are few reports of theranostics targeting the tumour microenvironment. Methods: Utilizing a newly developed bifunctional chelator, Lumi804, an anti-CD11b antibody (αCD11b) was readily labelled with either Zr-89 or Lu-177, yielding functional radiolabelled conjugates for PET, SPECT, and TRT. Findings: 89Zr/177Lu-labeled Lumi804-αCD11b enabled non-invasive imaging of TAMCs in murine gliomas. Additionally, 177Lu-Lumi804-αCD11b treatment reduced TAMC populations in the spleen and tumour and improved the efficacy of checkpoint immunotherapy. Interpretation: 89Zr- and 177Lu-labeled Lumi804-αCD11b may be a promising theranostic pair for monitoring and reducing TAMCs in gliomas to improve immunotherapy responses.},
doi = {10.1016/j.ebiom.2021.103571},
journal = {EBioMedicine},
number = C,
volume = 71,
place = {United States},
year = {Mon Sep 13 00:00:00 EDT 2021},
month = {Mon Sep 13 00:00:00 EDT 2021}
}
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