Synthesis and Preclinical Evaluation of a ⁶⁸Ga-Labeled Adnectin, ⁶⁸Ga-BMS-986192, as a PET Agent for Imaging PD-L1 Expression

Representative dot-plots of expression of green fluorescent protein and PD-L1 in wild-type U-698-M cells (A) and in U-698-M cells transduced by retroviral vector MP71 containing PD-L1 and green fluorescent protein (GFP) separated by P2A element (B).

Binding affinity and specificity of ⁶⁸Ga-BMS-986192 toward PD-L1 in competitive radioligand binding assays. (A) Cell-bound activity in presence of increasing concentrations of cold ligand (BXA-206362). (B) Cell-bound activity in presence of cold ligand (0.1 nM) on PD-L1–positive (gray bar) and PD-L1–negative (blue bar) U-698-M cells. IC₅₀ = half-maximal inhibitory concentration.

Dynamic ⁶⁸Ga-BMS-986192 PET/CT imaging in anesthetized PD-L1–positive and wild-type U-698-M xenograft–bearing NSG mice. (A) Summation maximum-intensity projections (MIP) of different time frames during 90-min acquisition. (B) Time–activity curves for blood pool (heart), kidneys, muscle, and PD-L1–positive tumor derived from dynamic data. (C) Axial PET/CT scan at 1 h after injection (p.i.).

(A) Static ⁶⁸Ga-BMS-986192 PET imaging examples in PD-L1–positive (yellow arrows) and wild-type (blue arrows) U-698-M xenograft–bearing NSG mice. Images are maximum-intensity projections (5–6 MBq, 4.5–5.5 μg) obtained at 1 and 2 h after injection (p.i.). Mouse at far right received ⁶⁸Ga-BMS-986192 plus blocking with unlabeled adnectin, 9 mg/kg. (B) ROI quantification of static PET scans (mean %ID/g).

(A) Axial ⁶⁸Ga-BMS-986192 PET scan at 1 h after injection in PD-L1–positive (yellow arrow) and wild-type (blue arrow) U-698-M xenograft–bearing NSG mouse. (B) Ex vivo FACS analysis of PD-L1 expression on wild-type (red) and PD-L1 transduced (blue) tumor cells. (C) Ex vivo hematoxylin–eosin (HE) and anti-PD-L1 immunohistochemistry (IHC) staining of PD-L1–positive and wild-type xenograft tissues.