A peptide-based 68Ga-PET radiotracer for imaging PD-L1 expression in cancer

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

Research output: Contribution to journalArticle

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, [68Ga]WL12, to detect PD-L1 expression in tumors noninvasively by positron emission tomography (PET). WL12, a cyclic peptide comprised of 14 amino acids, and it binds to PD-L1 with high affinity (Kd ~ 23 nM). Synthesis of [68Ga]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, MDAMB321, SUM149 and CHO tumors respectively at 1 h post-injection, with high binding specificity noted with co-injection of excess, non-radiolabeled WL12. PET imaging demonstrated high tissue contrast in all tumor models tested.

Original languageEnglish (US)
JournalMolecular Pharmaceutics
DOIs
Publication statusAccepted/In press - Apr 16 2018

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ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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