The key factors participating in angiogenesis include vascular endothelial growth factor (VEGF) and its receptors (VEGFRs), particularly VEGFR2. Angiogenesis suppression comprises the blocking of the VEGFR2 binding site by the monoclonal antibody ramucirumab (RAM). Our study focused on RAM radiolabelling with zirconium-89 along with subsequent in vitro and in vivo biological evaluation. RAM was conjugated with the bifunctional chelator p-SCN-Bn-deferoxamine (DFO) and subsequently radiolabelled with [⁸⁹Zr]Zr-oxalate. The binding affinity of [⁸⁹Zr]Zr-DFO-RAM to VEGFR2 was tested in vitro on prostate (PC-3) and ovary adenocarcinoma (SK-OV-3) cell lines. The positron emission tomography/computed tomography (PET/CT) imaging and ex vivo biodistribution experiments were performed in PC-3 and SK-OV-3 xenografted mice. The in vitro experiments revealed the preserved binding affinity of [⁸⁹Zr]Zr-DFO-RAM to VEGFR2. The obtained ex vivo biodistribution data showed the uptake in PC-3 and SK-OV-3 tumours at about 8.7 ± 0.2 and 12.1 ± 1.6%ID/g, respectively. The tumour-to-muscle ratio for 1, 3 and 6 days post injection was 3.9, 5.5 and 5.12 for PC-3 and 6.0, 8.0 and 8.82 for SK-OV-3 tumours, respectively. PET/CT images showed high radioactivity accumulation in the tumours starting already on the first day after tracer administration. The obtained results proved the potency of [⁸⁹Zr]Zr-DFO-RAM to target and image VEGFR2-positive tumours in vivo.

中文翻译：

---

锆89标记的抗VEGFR2单克隆抗体雷莫芦单抗用于肿瘤成像的临床前评价

参与血管生成的关键因素包括血管内皮生长因子（VEGF）及其受体（VEGFRs），特别是VEGFR2。血管生成抑制包括单克隆抗体雷莫芦单抗 (RAM) 阻断 VEGFR2 结合位点。我们的研究重点是用 zirconium-89 进行 RAM 放射性标记以及随后的体外和体内生物学评估。RAM 与双功能螯合剂p -SCN-Bn-去铁胺 (DFO) 结合，随后用 [ ⁸⁹ Zr]Zr-草酸盐进行放射性标记。^{[ 89}的结合亲和力Zr]Zr-DFO-RAM 对 VEGFR2 的体外测试在前列腺 (PC-3) 和卵巢腺癌 (SK-OV-3) 细胞系上进行。在 PC-3 和 SK-OV-3 异种移植小鼠中进行正电子发射断层扫描/计算机断层扫描 (PET/CT) 成像和离体生物分布实验。体外实验揭示了 [ ^{89 ] 保留的结合亲和力}Zr]Zr-DFO-RAM 转 VEGFR2。获得的离体生物分布数据显示，PC-3 和 SK-OV-3 肿瘤的摄取量分别约为 8.7 ± 0.2 和 12.1 ± 1.6% ID/g。PC-3 注射后 1、3 和 6 天的肿瘤与肌肉比率分别为 3.9、5.5 和 5.12，SK-OV-3 肿瘤分别为 6.0、8.0 和 8.82。PET/CT 图像显示，在示踪剂给药后的第一天就已经开始在肿瘤中积累高放射性。获得的结果证明了[ ⁸⁹ Zr]Zr-DFO-RAM 在体内靶向和成像VEGFR2阳性肿瘤的效力。