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

Autor: Elaine M. Jagoda PhD, Olga Vasalatiy PhD, Falguni Basuli PhD, Ana Christina L. Opina PhD, Mark R. Williams BS, Karen Wong MS, Kelly C. Lane BS, Steve Adler PhD, Anita Thein Ton MS, Lawrence P. Szajek PhD, Biying Xu PhD, Donna Butcher BS, Elijah F. Edmondson DVM, PhD, Rolf E. Swenson PhD, John Greiner PhD, James Gulley MD, PhD, Janet Eary MD, Peter L. Choyke MD
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Molecular Imaging, Vol 18 (2019)
Druh dokumentu: article
ISSN: 1536-0121
15360121
DOI: 10.1177/1536012119829986
Popis: Objective: 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. Methods: [ 89 Zr]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 [ 89 Zr]Zr-DFO-PD-L1 mAb without or with unlabeled avelumab (10, 20, 40, and 400 µg). Results: [ 89 Zr]Zr-DFO-PD-L1 mAb exhibited high affinity (K d ∼ 0.3 nM) and detected moderate PD-L1 expression levels in MDA-MB231 cells. The spleen and lymph nodes exhibited the highest [ 89 Zr]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 [ 89 Zr]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. Conclusions: [ 89 Zr]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. [ 89 Zr]Zr-DFO-PD-L1 mAb uptake in PD-L1+tumors increased with escalating doses of avelumab.
Databáze: Directory of Open Access Journals
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje