Evaluation of 89 Zr-Labeled Anti-PD-L1 Monoclonal Antibodies Using DFO and Novel HOPO Analogues as Chelating Agents for Immuno-PET

• Published in: ACS omega 2023-05, Vol.8 (19), p.17181-17194
• Main Authors: Radaram, Bhasker, Glazer, Sarah E, Yang, Ping, Li, Chia-Wei, Hung, Mien-Chie, Gammon, Seth T, Alauddin, Mian, Piwnica-Worms, David
• Format: Article
• Language: English
• ISSN: 2470-1343; 2470-1343
• DOI: 10.1021/acsomega.3c01547

Programmed death ligand 1 (PD-L1) is a type 1 transmembrane immunosuppressive protein that is expressed on a wide range of cell types, including cancer cells. Anti-PD-L1 antibodies have revolutionized cancer therapy and have led to improved outcomes for subsets of cancer patients, including triple-negative breast cancer (TNBC) patients. As a result, PET imaging of PD-L1 protein expression in cancer patients has been explored for noninvasive detection of PD-L1 expressing tumors as well as monitoring response to anti-PD-L1 immune checkpoint therapy. Previous studies have indicated that the stability and target detection of antibody-based radio-conjugates can be dramatically affected by the chelator used. These reports demonstrated that the chelator HOPO diminishes Zr de-chelation compared to DFO. Herein, we report an improved HOPO synthesis and evaluated a series of novel analogues for thermal stability, serum stability, PD-L1-specific binding using the BT-549 TNBC cell line, PET imaging , as well as biodistribution of Zr-labeled anti-PD-L1 antibodies in BT-549 xenograft murine models. A new chelator, C5HOPO, demonstrated high stability and afforded effective PD-L1 targeting immuno-PET. These results demonstrated that an improved HOPO chelator is an effective chelating agent that can be utilized to image therapeutically relevant targets .