The mixed patient responses to antibodies targeting immune checkpoint proteins (e.g., CTLA-4, PD-1, PD-L1) have generated tremendous interest in discovering biomarkers that predict which patients will best respond to these treatments. To complement molecular biomarkers obtained from biopsies, the nuclear medicine community has begun developing radiopharmaceuticals that may provide a more holistic assessment of the biological character of all disease sites in patients. On the leading edge of clinical translation are a spectrum of radiolabeled antibodies targeting immune checkpoint proteins or T cell-specific antigens. The adoption of these reagents requires development of efficient and versatile methods for antibody bioconjugation and radiochemistry. We report herein protocols for the preparation of an anti-PD-L1 IgG1 (termed C4) labeled with zirconium-89. The approach is time and cost economical, high yielding, and adaptable to numerous antibody clones and platforms of interest to the immune-oncology community. Included also are representative methods for characterizing the pharmacology of the antibody post bioconjugation, and conducting an in vivo assessment of radiotracer biodistribution in tumor bearing mouse models.
Keywords: Biomarker; Cancer immunotherapy; Molecular imaging; Positron emission tomography; Radiochemistry.
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