Immuno-SPECT/PET Imaging with Radioiodinated Anti-PD-L1 Antibody to Evaluate PD-L1 Expression in Immune-competent Murine Models and PDX Model of Lung Adenocarcinoma

Objective: Accurate evaluation of tumor programmed death ligand 1 (PD-L1) expression can assist in predicting whether a patient will respond to anti-PD-L1 therapy. In this study, we aimed to develop stable radioiodinated PD-L1 antibodies that can be used for PD-L1 targeted SPECT/PET imaging.

Methods: Radioiodination was accomplished via a prosthetic group ([I]SIB or [I]SIB) to give radioiodinated anti-human PD-L1 and anti-mouse PD-L1 antibody (anti-PD-L1 and anti-PD-L1). MicroSPECT/PET imaging and biodistribution of radioiodinated antibodies were studied in two immune-competent murine models (B16F10 and 4T1 syngeneic tumor models) and patient-derived xenograft (PDX) model of lung adenocarcinoma to evaluate the feasibility of identifying tumor PD-L1 expression.

Results: Radioiodinated PD-L1 antibodies had high radiochemical purity (>99%) and favorable stability in vivo. There was high uptake of [I]SIB-anti-PD-L1 in both 4T1 and B16F10 syngeneic tumors when injected with 5.5 MBq radiotracers containing 200 μg anti-mouse-PD-L1. The presence of excess unlabeled anti-PD-L1 antibody increased [I]SIB-anti-PD-L1 uptake in tumors. The highly specific PD-L1-positive tumor uptake detected by SPECT imaging indicated that radioiodinated antibody could be used for PD-L1 expression imaging. In addition, PET imaging of the PDX model was performed with [I]SIB-anti-PD-L1, which showed high signal intensity in tumors and optimal contrast between tumor and muscle (tumor-to-muscle ratios at 6 h p.i. and 24 h p.i. were 2.5 and 5.3, respectively).

Conclusions: This study provides an efficient strategy for synthesizing stable radioiodinated PD-L1 antibodies with excellent pharmacokinetics to identify PD-L1 expression in tumors.