Dataset Information

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.

Funding

A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

SUBMITTER: Foster A

PROVIDER: S-EPMC8446777 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Publications

Novel theranostic agent for PET imaging and targeted radiopharmaceutical therapy of tumour-infiltrating immune cells in glioma.

Foster Alexandra A Nigam Shubhanchi S Tatum David S DS Raphael Itay I Xu Jide J Kumar Rajeev R Plakseychuk Elizabeth E Latoche Joseph D JD Vincze Sarah S Li Bo B Giri Rajan R McCarl Lauren H LH Edinger Robert R Ak Murat M Peddagangireddy Vishal V Foley Lesley M LM Hitchens T Kevin TK Colen Rivka R RR Pollack Ian F IF Panigrahy Ashok A Magda Darren D Anderson Carolyn J CJ Edwards W Barry WB Kohanbash Gary G

EBioMedicine 20210913

<h4>Background</h4>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<sup>+</sup> 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 ther ...[more]

PMID: 34530385

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Dataset Information

Novel theranostic agent for PET imaging and targeted radiopharmaceutical therapy of tumour-infiltrating immune cells in glioma.

Background

Methods

Findings

Interpretation

Funding

Publications

Novel theranostic agent for PET imaging and targeted radiopharmaceutical therapy of tumour-infiltrating immune cells in glioma.

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