Immuno-PET Imaging of the Programmed Cell Death-1 Ligand (PD-L1) Using a Zirconium-89 Labeled Therapeutic Antibody, Avelumab

Author:

Jagoda, Elaine M

Vasalatiy, Olga

Basuli, Falguni

Opina, Ana Christina L

Williams, Mark R

Wong, Karen

Lane, Kelly C

Adler, Steve

Ton, Anita Thein

Szajek, Lawrence P

Xu, Biying

Butcher,Donna

Edmondson,Elijah

Swenson, Rolf E

Greiner, John

Gulley,James

Eary, Janet

Choyke, Peter L
Author Address

1 Molecular Imaging Program, National Cancer Institute, Bethesda, MD, USA., 2 Imaging Probe Development Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, MD, USA., 3 PET Department, Clinical Center, NIH, Bethesda, MD, USA., 4 Pathology & Histotechnology Lab Frederick National Laboratory for Cancer Research, NCI, Frederick, MD, USA., 5 Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda, MD, USA., 6 Genitourinary Malignancies Branch, National Cancer Institute, Bethesda, MD, USA., 7 Clinical Research Directorate/CMRP, Leidos Biomedical Research Inc. (formerly SAIC-Frederick, Inc.), Frederick National Laboratory for Cancer Research, Frederick, MD, USA., 8 Cancer Imaging Program, National Cancer Institute, Bethesda, MD, USA.,

Abstract:

The goal is to evaluate avelumab, an anti-PD-L1 monoclonal immunoglobulin G antibody labeled with zirconium-89 in human PD-L1-expressing cancer cells and mouse xenografts for clinical translation. [89Zr]Zr-DFO-PD-L1 monoclonal antibody (mAb) was synthesized using avelumab conjugated to desferrioxamine. In vitro binding studies and biodistribution studies were performed with PD-L1+MDA-MB231 cells and MDA-MB231 xenograft mouse models, respectively. Biodistributions were determined at 1, 2, 3, 5, and 7 days post coinjection of [89Zr]Zr-DFO-PD-L1 mAb without or with unlabeled avelumab (10, 20, 40, and 400 µg). [89Zr]Zr-DFO-PD-L1 mAb exhibited high affinity (Kd ~ 0.3 nM) and detected moderate PD-L1 expression levels in MDA-MB231 cells. The spleen and lymph nodes exhibited the highest [89Zr]Zr-DFO-PD-L1 mAb uptakes in all time points, while MDA-MB231 tumor uptakes were lower but highly retained. In the unlabeled avelumab dose escalation studies, spleen tissue-muscle ratios decreased in a dose-dependent manner indicating specific [89Zr]Zr-DFO-PD-L1 mAb binding to PD-L1. In contrast, lymph node and tumor tissue-muscle ratios increased 4- to 5-fold at 20 and 40 µg avelumab doses. [89Zr]Zr-DFO-PD-L1 mAb exhibited specific and high affinity for PD-L1 in vitro and had target tissue uptakes correlating with PD-L1 expression levels in vivo. [89Zr]Zr-DFO-PD-L1 mAb uptake in PD-L1+tumors increased with escalating doses of avelumab.

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