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

Autor: Rajeev Kumar, Bo Li, Lauren McCarl, Elizabeth Plakseychuk, Ian F. Pollack, Itay Raphael, Shubhanchi Nigam, David S. Tatum, Carolyn J. Anderson, Sarah Vincze, Joseph D. Latoche, T. Kevin Hitchens, Alexandra Foster, Darren Magda, Jide Xu, W. Barry Edwards, Robert S. Edinger, Gary Kohanbash, Rivka R. Colen, Vishal Peddagangireddy, Ashok Panigrahy, Lesley M. Foley, Rajan Giri, Murat Ak
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Medicine (General)
medicine.medical_treatment
Lutetium
Multimodal Imaging
Mice
Tumor-Associated Macrophages
bifunctional chelator
Tumor Microenvironment
Molecular Targeted Therapy
Immune Checkpoint Inhibitors
Therapeutic strategy
biology
checkpoint immunotherapy
Disease Management
General Medicine
Glioma
medicine.anatomical_structure
Medicine
Bifunctional chelator
Disease Susceptibility
Antibody
immunoPET
Research Paper
Spleen
General Biochemistry
Genetics and Molecular Biology
Immunophenotyping
Immune system
Lymphocytes
Tumor-Infiltrating
R5-920
targeted radiotherapy
Cell Line
Tumor
medicine
Biomarkers
Tumor
Animals
Humans
Radioisotopes
business.industry
Immunotherapy
Pet imaging
medicine.disease
Theranostics
Xenograft Model Antitumor Assays
gliomas
Disease Models
Animal
Positron-Emission Tomography
Cancer research
biology.protein
Zirconium
Radiopharmaceuticals
business
Zdroj: EBioMedicine, Vol 71, Iss, Pp 103571-(2021)
EBioMedicine
ISSN: 2352-3964
Popis: 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.
Graphical abstract Image, graphical abstract
Databáze: OpenAIRE
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