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

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.

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.

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.

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