Rohollahi Zahra, Aghamiri Seyed Mahmoud Reza, Yousefnia Hassan, Alirezapour Behrouz, Moghaddasi Ali, Zolghadri Samaneh
Department of Medical Radiation Engineering, Shahid Beheshti University, Tehran, Iran.
Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), Tehran, Iran.
Curr Radiopharm. 2025;18(2):131-140. doi: 10.2174/0118744710326742241018050220.
An early diagnosis of cancer can lead to choosing more effective treatment and increase the number of cancer survivors. In this study, the preparation and preclinical aspects of [Zr]Zr-DFO-Rituximab, a high-potential agent for PET imaging of Non- Hodgkin Lymphoma (NHL), were evaluated.
DFO was conjugated to rituximab monoclonal antibody (mAb), and DFO-rituximab was successfully labeled with zirconium-89 (Zr) at optimized conditions. The stability of the complex was assessed in human blood serum and PBS buffer. Radioimmunoreactivity (RIA) of the radioimmunoconjugate (RIC) was evaluated on CD20-overexpressing Raji cell line and CHO cells. The biodistribution of the radiolabeled mAb was studied in normal and tumorbearing rodents. Finally, the absorbed dose in human organs was estimated.
The radiolabeled compound was prepared with radiochemical purity (RCP) >99% (RTLC) and a specific activity of 180±1.8 GBq/g. The RCP of the final complex PBS buffer and human blood serum was higher than 95%, even after 48 h post incubation. The RIA assay demonstrated that more than 63% of the radiolabeled compound (40 ng/ml, 0.5 mL) was bound to 5×10 Raji cells. The biodistribution of the final product in tumor-bearing mice showed a high accumulation of the RIC in the tumor site in all intervals post-injection. Tumor/non-target ratios were increased over time, and longer imaging time was suggested. The dosimetry data indicated that the liver received the most absorbed dose after the complex injection.
[Zr]Zr-DFO-Rituximab represents a significant advancement in the field of oncological imaging and offers a robust platform for both diagnostic and therapeutic applications in the management of B-cell malignancies.
癌症的早期诊断有助于选择更有效的治疗方法，并增加癌症幸存者的数量。在本研究中，对[Zr]Zr-DFO-利妥昔单抗（一种用于非霍奇金淋巴瘤（NHL）PET成像的高潜力药物）的制备和临床前方面进行了评估。
将去铁胺（DFO）与利妥昔单抗单克隆抗体（mAb）偶联，并在优化条件下用锆-89（Zr）成功标记DFO-利妥昔单抗。在人血清和磷酸盐缓冲盐水（PBS）缓冲液中评估复合物的稳定性。在过表达CD20的拉吉细胞系和中国仓鼠卵巢（CHO）细胞上评估放射免疫缀合物（RIC）的放射免疫反应性（RIA）。在正常和荷瘤啮齿动物中研究放射性标记单克隆抗体的生物分布。最后，估计人体器官的吸收剂量。
制备的放射性标记化合物的放射化学纯度（RCP）>99%（薄层层析），比活度为180±1.8 GBq/g。即使在孵育48小时后，最终复合物在PBS缓冲液和人血清中的RCP仍高于95%。RIA分析表明，超过63%的放射性标记化合物（40 ng/ml，0.5 mL）与5×10拉吉细胞结合。最终产物在荷瘤小鼠中的生物分布显示，在注射后的所有时间段内，RIC在肿瘤部位均有高度蓄积。肿瘤/非靶标比值随时间增加，建议延长成像时间。剂量学数据表明，复合物注射后肝脏接受的吸收剂量最高。
[Zr]Zr-DFO-利妥昔单抗代表了肿瘤成像领域的一项重大进展，并为B细胞恶性肿瘤的管理提供了一个强大的诊断和治疗应用平台。
