Noninvasive evaluation of PD-L1 expression using Copper 64 labeled peptide WL12 by micro-PET imaging in Chinese hamster ovary cell tumor model

Bioorg Med Chem Lett. 2021 May 15:40:127901. doi: 10.1016/j.bmcl.2021.127901. Epub 2021 Mar 8.

Abstract

As an indicative biomarker for immunotherapy, PD-L1 plays an important role in the clinical decision-making of the immune checkpoint blockade therapy. PET imaging through radiotracer can real-timely, quantitatively, and non-invasively assess the expression of PD-L1 in tumors. Here, we reported a copper-64 radiolabeled NOTA-WL12, 64Cu-NOTA-WL12, and preliminarily evaluated its application in non-invasively detecting the PD-L1 expression.64Cu-NOTA-WL12 was produced with high radiochemical yield (>90%), radiochemical purity (>98%), and specific activity (20 MBq/nmol). 64Cu-NOTA-WL12 showed high in vitro stability and high binding affinity to the PD-L1 (KD ≈ 3.012 nM). The micro-positron emission tomography/computerized tomography (micro-PET/CT) imaging indicated that 64Cu-NOTA-WL12 was specifically accumulated in the tumor with PD-L1 expression. All results demonstrated that 64Cu-NOTA-WL12 holds great potential for noninvasive evaluation of PD-L1 expression levels.

Keywords: (64)Cu-NOTA-WL12; PD-L1; PET/CT imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7-H1 Antigen / analysis*
  • B7-H1 Antigen / genetics*
  • CHO Cells
  • Copper Radioisotopes / economics*
  • Cricetulus
  • Gene Expression
  • Humans
  • Neoplasms, Experimental
  • Peptides / chemistry*
  • Positron Emission Tomography Computed Tomography
  • Protein Binding
  • Radiopharmaceuticals / chemistry*
  • Staining and Labeling
  • Structure-Activity Relationship

Substances

  • B7-H1 Antigen
  • Copper Radioisotopes
  • Copper-64
  • Peptides
  • Radiopharmaceuticals