Novel theranostic agent for PET imaging and targeted radiopharmaceutical therapy of tumour-infiltrating immune cells in glioma
Alexandra Foster, Shubhanchi Nigam, David S. Tatum, Itay Raphael, Jide Xu, Rajeev Kumar, Elizabeth Plakseychuk, Joseph D. Latoche, Sarah Vincze, Bo Li, Rajan Giri, Lauren McCarl, Robert S. Edinger, Murat Ak, Vishal Peddagangireddy, Lesley M. Foley, T. Kevin Hitchens, Rivka R. Colen, Ian F. Pollack, Ashok Panigrahy, Darren Magda, Carolyn J. Anderson, Wilson B. Edwards, Gary Kohanbash
Abstract
BACKGROUND: 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: Lu-Lumi804-αCD11b treatment reduced TAMC populations in the spleen and tumour and improved the efficacy of checkpoint immunotherapy. INTERPRETATION: Lu-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.