Development of a Specifically Labeled 89 Zr Antibody for the Noninvasive Imaging of Tumors Overexpressing B7-H3

作者：Meng Zheng, Qingfeng Liu, Hua Zhang, Yanan Wang, Yanan Wang, Kaijie Zhang, Huiwen Mu, Fengqing Fu, Xueguang Zhang, Yan Wang, Yan Wang, Liyan Miao · 发表于：Molecular Pharmaceutics · 年份：2024 · DOI：10.1021/acs.molpharmaceut.4c00597 · 被引用次数：6 · 研究领域：Radiopharmaceutical Chemistry and Applications、Medical Imaging and Pathology Studies、Medical Imaging Techniques and Applications

B7-H3 has emerged as a promising target and potential biomarker for diagnosing tumors, evaluating treatment efficacy, and determining patient prognosis. Hu4G4 is a recombinant humanized antibody that selectively targets the extracellular domain of human B7-H3. In this study, we describe the radiolabeling of hu4G4 with the positron emission tomography (PET) emitter radionuclide zirconium 89 ( 89 Zr) and evaluate its potency as an immuno-PET tracer for B7-H3-targeted imaging by comparing it in vitro and in vivo to [ 89 Zr]Zr-DFO–DS-5573a using various models. The radiolabeled compound, [ 89 Zr]Zr-desferrioxamine-hu4G4 ([ 89 Zr]Zr-DFO-hu4G4), demonstrated a high radiochemical purity (RCP) of greater than 99% and a specific activity of 74 MBq/mg following purification. Additionally, it maintained stability in human serum albumin (HSA) and acetate buffer, preserving over 90% of its RCP after 7 days. Three cell lines targeting human B7-H3(U87/CT26 -CD276 /GL261 -CD276 ) were used. Flow cytometry analysis indicated that the B7-H3-positive cells (U87/CT26 -CD276 /GL261 -CD276 ) had a higher B7-H3 protein level with no expression in the B7-H3-negative cells (CT26 -wt /GL261 -wt ) ( P < 0.001). Moreover, the cellular uptake was 45.71 ± 3.78% for [ 89 Zr]Zr-DFO-hu4G4 in CT26 -CD276 cells versus only 0.93 ± 0.47% in CT26 -wt cells and 30.26 ± 0.70% when [ 89 Zr]Zr-DFO-hu4G4 in CT26 -CD276 cells were blocked with 100× 8H9. The cellular uptake of [ 89 Zr]Zr-DFO-hu4G4 was akin to that obser...