Peptide-Based 68 Ga-PET Radiotracer for Imaging PD-L1 Expression in Cancer

Ravindra A. De Silva, Dhiraj Kumar, Ala Lisok, Samit Chatterjee, Bryan Wharram, Kalagadda Venkateswara Rao, Ronnie Mease, Robert F. Dannals, Martin G. Pomper, Sridhar Nimmagadda

Research output: Contribution to journalArticlepeer-review

Abstract

Tumors create and maintain an immunosuppressive microenvironment that promotes cancer cell escape from immune surveillance. The immune checkpoint protein programmed death-ligand 1 (PD-L1) is expressed in many cancers and is an important contributor to the maintenance of the immunosuppressive tumor microenvironment. PD-L1 is a prominent target for cancer immunotherapy. Guidance of anti-PD-L1 therapy is currently effected through measurement of PD-L1 through biopsy and immunohistochemistry. Here, we report a peptide-based imaging agent, [ 68 Ga]WL12, to detect PD-L1 expression in tumors noninvasively by positron emission tomography (PET). WL12, a cyclic peptide comprising 14 amino acids, binds to PD-L1 with high affinity (IC50 23 nM). Synthesis of [ 68 Ga]WL12 provided radiochemical purity >99% after purification. Biodistribution in immunocompetent mice demonstrated 11.56 ± 3.18, 4.97 ± 0.8, 1.9 ± 0.1, and 1.33 ± 0.21 percentage of injected dose per gram (%ID/g) in hPD-L1, MDAMB231, SUM149, and CHO tumors, respectively, at 1 h postinjection, with high binding specificity noted with coinjection of excess, nonradiolabeled WL12. PET imaging demonstrated high tissue contrast in all tumor models tested.

Original languageEnglish (US)
Pages (from-to)3946-3952
Number of pages7
JournalMolecular Pharmaceutics
Volume15
Issue number9
DOIs
StatePublished - Sep 4 2018

Keywords

  • NSCLC
  • PD-1
  • TNBC
  • immune checkpoint therapy
  • peptide

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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