Immunotherapy for the treatment of cancer is rapidly evolving from therapies that globally and nonspecifically simulate the immune system to more targeted activation of individual components of the immune system. More specifically, therapies that inhibit the interaction between programmed death ligand 1 (PD-L1), present on the surface of tumor or antigen-presenting cells, and programmed death 1 (PD-1), present on the surface of activated lymphocytes, are generating much excitement and enthusiasm, even in malignancies that are not traditionally considered to be immunogenic. Developing new methods to predict which patients will respond to a given immunotherapy is a “holy grail” for the field. Currently, biopsy and immunohistochemistry is used to determine antigen status of the tumor. However, in the case of PD-L1, it is well established that not patients whose biopsy is PD-L1 positive will respond to anti-PD-L1 therapy, and some patients with PD-L1 negative biopsies experience durable responses. Lastly, how or if PD-L1 expression changes over the lifetime of a tumor cell is not clear. These observations call into question whether studying an archival biopsy of a single lesion in a patient with substantial and evolving tumor burden is the best manner in which to study the utility of tumor expression of PDL1 as a predictive biomarker for anti-PDL1 therapy. We proposed instead to develop an immunoPET assay to globally quantify expression of PDL1 in tumors over time. In collaboration with investigators at the Singapore Immunology Network, we have radiolabeled a recombinant human monoclonal IgG with zirconium-89 and studied its pharmacology in vitro and in vivo. Conjugation of the antibody to desferrioxamine did not compromise the affinity or immunoreactivity of the IgG. The DFO-IgG conjugate was radiolabeled to>80% radiochemical yield and>99% purity. The 89Zr-IgG specifically targeted multiple PDL1 positive melanoma and non-small cell lung cancer xenografts in vivo. Moreover, the 89Zr-IgG did not appreciably localize to PDL1 negative tumor cells. In summary, these data highlight the ability of 89Zr-immunoPET to establish PDL1 status on a tumor cell, and argue strongly for a first in man study.