copper Cu 64-DOTA-pembrolizumab

A radioimmunoconjugate composed of pembrolizumab, a humanized monoclonal immunoglobulin (Ig) G4 antibody directed against the human cell surface receptor programmed cell death 1 (PD-1; PDCD1; CD279; programmed cell death-1), conjugated with the bifunctional, macrocyclic chelating agent 1,4,7,10-tetra-azacyclododecane-1,4,7,10-tetra-acetic acid (DOTA) and labeled with the radioisotope copper Cu 64, with potential diagnostic properties upon positron emission tomography (PET) imaging. Upon administration, the monoclonal antibody moiety of copper Cu 64-DOTA-pembrolizumab specifically binds to PD-1, an inhibitory signaling receptor expressed on the surface of activated T cells, and blocks the binding to and activation of PD-1 by its ligands. Upon PET imaging, PD-1-expressing T cells, as well as pembrolizumab biodistribution, can be visualized and the expected response to treatment with pembrolizumab, as well as selection of patients that would respond to pembrolizumab, can be assessed. The ligands for PD-1 include programmed cell death-1 ligand 1 (PD-L1), which is overexpressed on certain cancer cells, and programmed cell death-1 ligand 2 (PD-L2), which is primarily expressed on antigen-presenting cells (APCs). Activated PD-1 negatively regulates T-cell activation and plays a key role in tumor evasion from host immunity.