18F-BMS-986229 PET imaging of tumor PD-L1 expression in glioblastoma patients.

Abstract

Background: Neurooncologists urgently need biomarkers that can optimize the clinical development of PD-L1 targeted immunotherapy in the treatment of glioblastoma. This study evaluated PD-L1 targeted tumor imaging by positron emission tomography (PET) in glioblastoma patients, using the novel macrocyclic peptide radiotracer ¹⁸F-BMS-986229.

Results: Twelve adult postsurgical glioblastoma patients underwent brain PET imaging 1-hour post injection 190±20 MBq of ¹⁸F-BMS-986229. In a subset of patients, dynamic PET scans were obtained for pharmacokinetic modeling in tumors and normal tissues. Tracer kinetics in both tumor sites and normal tissues were well described by a reversible 1-tissue compartment model. Tumor sites demonstrated ¹⁸F-BMS-986229 tracer-avidity (SUV = 1.1 ± 0.4; range, 0.6-1.7) in 10 of 12 cases, with negligible tracer-avidity in normal brain structures. Tumor avidity for ¹⁸F-BMS-986229 on PET was spatially independent of tumor contrast-enhancement on magnetic resonance imaging, indicating that tracer-binding at tumor site was not dependent upon blood-brain barrier breakdown. The observed tumor site low tracer-uptake paralleled low immunohistochemical PD-L1 expression in resected tumors, with no correlations between standardized uptake value versus tumor MGMT methylation, PTEN oncogenic mutation status, tumor mutation burden, or patient overall survival.

Conclusion: This pilot study demonstrates the feasibility of characterizing tumor sites in glioblastoma patients by PD-L1-targeted PET imaging with¹⁸F-BMS-986229, even in patients with low tumor PD-L1 expression. We hypothesize that ¹⁸F-BMS-986229 PET can improve the pharmacometrics of PD-L1-targeted therapy trials.

Trial registration number: NCT02617589. Trial Registration Date: December 1st, 2015.