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

Journal Article · · EBioMedicine
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  1. Univ. of Pittsburgh, PA (United States); OSTI
  2. Univ. of Pittsburgh, PA (United States)
  3. Lumiphore, Inc., Berkeley, CA (United States)
  4. Univ. of Missouri, Columbia, MO (United States)
  5. Univ. of Pittsburgh, PA (United States); Univ. of Missouri, Columbia, MO (United States)
+ Show Author Affiliations
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.
Research Organization:
Univ. of Pittsburgh, PA (United States)
Sponsoring Organization:
UPMC Hillman Cancer Center; USDOE Office of Science (SC), Nuclear Physics (NP)
OSTI ID:
1904053
Journal Information:
EBioMedicine, Journal Name: EBioMedicine Journal Issue: C Vol. 71; ISSN 2352-3964
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
English

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Related Subjects

60 APPLIED LIFE SCIENCES
bifunctional chelator
checkpoint immunotherapy
gliomas
immunoPET
targeted radiotherapy
theranostics