Imaging PD-L1 Expression with ImmunoPET

Truillet C, et al., 29(1):96-103, Bioconjug Chem., 2018

Described herein is the development and characterization of a new recombinant human antibody (C4) that potently binds an extracellular epitope on human and mouse immune checkpoint protein, PD-L1. Furthermore, C4 antibody was radio labeled with zirconium-89 and used to measure PD-L1 expression levels in vivo with immunoPET. Binding kinetics of C4 antibody against human and mouse PD-L1 were investigated using Bio-Layer Interferometry (BLI). A Pall ForteBio Octet RED384 instrument equipped with Anti-Human IgG Fc (AHQ) Biosensor probes was used to perform BLI experiments. AHQ sensor tips were immobilized with C4 antibody. The association and dissociation kinetics of human and mouse PD-L1 was measured by immersing the C4 antibody loaded biosensor probes into various concentrations of human and mouse PD-L1 samples. In between each sample measurement, the Biosensor surfaces were regenerated by exposing them to a regeneration buffer (glycine pH 1.5). Data obtained were analyzed by using a 1:1 binding model. Kinetic constants and equilibrium dissociation constants were determined. Overall results of this study demonstrate that low levels of PD-L1 expressed in cancer models can be imaged with immunoPET using the novel recombinant human antibody.

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