High-Resolution PET Imaging with Therapeutic Antibody-based PD-1/PD-L1 Checkpoint Tracers

Theranostics. 2016 Jun 18;6(10):1629-40. doi: 10.7150/thno.15253. eCollection 2016.


Checkpoint-blocking antibodies like those targeting the PD-1/PD-L1 pathway have revolutionized oncology. We developed radiotracers based on therapeutic checkpoint-blocking antibodies permitting sensitive and high-resolution PET imaging of both PD-1 and PD-L1 in immunocompetent mice. ImmunoPET of naive mice revealed similar overall expression patterns for PD-1 and PD-L1 in secondary lymphoid organs (spleen and lymph nodes). Interestingly, PD-L1 was also detected in brown adipose tissue (BAT), confirming the notion that BAT is immunologically relevant. Under pathophysiological conditions, strong expression of the receptor/ligand pair was also found in non-lymphoid tissues. Both were specifically detected in malignant tumors. PD-1 was readily detected after combined immunoradiotherapy causing massive tumor infiltration by PD-1+ lymphocytes. PD-L1 tracer uptake was reduced in PD-L1 knockout tumors. Moreover, monitoring the expression changes of PD-L1 in response to its main inducer, the effector T cell cytokine IFN-γ, revealed robust upregulation in the lung. This suggests that T cell responses in the lung, a vital organ continuously exposed to a variety of antigens, are strongly restrained by the PD-1 checkpoint. In turn, this could explain the association of PD-1 checkpoint inhibition with potentially fatal immune-mediated pneumonitis and partially also its efficacy in lung cancer.

Keywords: PD-1/PD-L1 checkpoint; PET; antibody imaging.; non-invasive imaging.

MeSH terms

  • Animals
  • Antibodies / administration & dosage*
  • B7-H1 Antigen / analysis*
  • B7-H1 Antigen / immunology
  • Immunologic Factors / administration & dosage*
  • Mice
  • Positron-Emission Tomography / methods*
  • Programmed Cell Death 1 Receptor / analysis*
  • Programmed Cell Death 1 Receptor / immunology


  • Antibodies
  • B7-H1 Antigen
  • Cd274 protein, mouse
  • Immunologic Factors
  • Pdcd1 protein, mouse
  • Programmed Cell Death 1 Receptor