Xu Yuping, Wang Lizhen, Pan Donghui, Yan Junjie, Wang Xinyu, Yang Runlin, Li Mingzhu, Liu Yu, Yang Min
Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, 214063, Jiangsu, China.
Nanjing Medical University, Nanjing, 210029, Jiangsu, China.
EJNMMI Res. 2020 Jun 3;10(1):58. doi: 10.1186/s13550-020-00649-7.
Human epidermal growth factor receptor-2 (HER2) is an essential biomarker for tumor treatment. Affibody is an ideal vector for preparing HER2 specific probes because of high affinity and rapid clearance from normal tissues, etc. Zirconium-89 is a PET imaging isotope with a long half-life and suitable for monitoring biological processes for more extended periods. In this study, a novel Zr-labeled HER2 affibody, [Zr]Zr-DFO-MAL-Cys-MZHER2, was synthesized, and its imaging characters were also assessed.
The precursor, DFO-MAL-Cys-MZHER2, was obtained with a yield of nearly 50%. The radiochemical yield of [Zr]Zr -DFO-MAL-Cys-MZHER2 was 90.2 ± 1.9%, and the radiochemical purity was higher than 95%. The total synthesis time was only 30 min. The probe was stable in PBS and serum. The tracer accumulated in HER2 overexpressing human ovarian cancer SKOV-3 cells. In vivo studies in mice bearing tumors showed that the probe was highly retained in SKOV-3 xenografts even for 48 h. The tumors were visualized with good contrast to normal tissues. ROI analysis revealed that the average uptake values in the tumor were greater than 5% IA/g during 48 h postinjection. On the contrary, the counterparts of MCF-7 tumors kept low levels ( ~ 1% IA/g). The outcome was consistent with the immunohistochemical analysis and ex vivo autoradiography. The probe quickly cleared from the normal organs except kidneys and mainly excreted through the urinary system.
The novel HER2 affibody for PET imaging was easily prepared with satisfactory labeling yield and radiochemical purity. [Zr]Zr-DFO-MAL-Cys-MZHER2 is a potential candidate for detecting HER2 expression. It may play specific roles in clinical cancer theranostics.
人表皮生长因子受体2（HER2）是肿瘤治疗的重要生物标志物。亲和体因其具有高亲和力以及能从正常组织快速清除等特点，是制备HER2特异性探针的理想载体。锆-89是一种具有长半衰期的正电子发射断层显像（PET）成像同位素，适用于更长时间监测生物过程。在本研究中，合成了一种新型的锆标记HER2亲和体[Zr]Zr-DFO-MAL-Cys-MZHER2，并评估了其成像特性。
获得了前体DFO-MAL-Cys-MZHER2，产率接近50%。[Zr]Zr-DFO-MAL-Cys-MZHER2的放射化学产率为90.2±1.9%，放射化学纯度高于95%。总合成时间仅30分钟。该探针在磷酸盐缓冲盐水（PBS）和血清中稳定。示踪剂在HER2过表达的人卵巢癌SKOV-3细胞中积累。在荷瘤小鼠体内研究表明，该探针即使在48小时内仍高度保留在SKOV-3异种移植瘤中。肿瘤与正常组织形成良好对比得以可视化。感兴趣区（ROI）分析显示，注射后48小时内肿瘤的平均摄取值大于5%注射活度（IA）/克。相反，MCF-7肿瘤的摄取值保持在低水平（约1%IA/克）。该结果与免疫组织化学分析和离体放射自显影一致。除肾脏外，该探针能迅速从正常器官清除，主要通过泌尿系统排泄。
这种新型的用于PET成像的HER2亲和体易于制备，标记产率和放射化学纯度令人满意。[Zr]Zr-DFO-MAL-Cys-MZHER2是检测HER2表达的潜在候选物。它可能在临床癌症诊疗中发挥特定作用。
