Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Korea.
Ann Nucl Med. 2021 May;35(5):639-647. doi: 10.1007/s12149-021-01607-6. Epub 2021 Apr 3.
The aim of this study was to evaluate the radiation dosimetry of alpha-emitter Ac-DOTA-rituximab using Monte Carlo simulation of Cu-DOTA-rituximab.
CD20 expression was evaluated in lymphoma cell lines (Jurkat and Raji). DOTA-rituximab was conjugated and then chelated by Cu. Tumor xenograft models were established in BALB/c-nu mice. Animal PET/CT imaging was obtained after tail vein injection with and without a pre-dose of 2 mg of cold rituximab. Specific binding of tumors was evaluated by an organ distribution assay and autoradiography. CD20 expression in tumor tissues was evaluated by immunohistochemistry. The residence time was calculated using Cu-DOTA-rituximab PET/CT acquisition data using OLINDA/EXM software. Ac-DOTA-rituximab tumor dosimetry was performed using Monte Carlo simulation with Cu-DOTA-rituximab PET/CT images.
Specific binding of Raji cells (CD20 positive) was 90 times that of Jurkat cells (CD20 negative) (p < 0.0001). Immunoreactivity was more than 75%. PET/CT imaging with Cu-DOTA-rituximab was specifically observed in tumors. The radioactivity of the tumor was much higher than that of other organs, and tumor uptake was related to CD20 expression. The predicted human dose for the administration of Cu-DOTA-rituximab was measured as the effective dose (1.07E-02 mSv/MBq). In the tumor region, equivalent doses of Ac-DOTA-rituximab (14 Sv/MBq) were much higher (74-fold) than those of Cu-DOTA-rituximab (0.19 Sv/MBq) (p < 0.01).
Tumor dosimetry of Ac-DOTA-rituximab can be estimated via the Monte Carlo simulation of Cu-DOTA-rituximab. Ac-DOTA-rituximab can be employed for lymphoma as targeted alpha therapy.
本研究旨在通过铜-DOTA-利妥昔单抗的蒙特卡罗模拟来评估α发射器 Ac-DOTA-利妥昔单抗的辐射剂量学。
评估了淋巴瘤细胞系（Jurkat 和 Raji）中的 CD20 表达。DOTA-利妥昔单抗被缀合，然后用 Cu 螯合。在 BALB/c-nu 小鼠中建立肿瘤异种移植模型。尾静脉注射和不注射 2mg 冷利妥昔单抗后，进行动物 PET/CT 成像。通过器官分布测定和放射自显影评估肿瘤的特异性结合。通过免疫组织化学评估肿瘤组织中的 CD20 表达。使用 OLINDA/EXM 软件，根据 Cu-DOTA-利妥昔单抗 PET/CT 采集数据计算停留时间。使用 Monte Carlo 模拟，根据 Cu-DOTA-利妥昔单抗 PET/CT 图像进行 Ac-DOTA-利妥昔单抗肿瘤剂量学。
Raji 细胞（CD20 阳性）的特异性结合是 Jurkat 细胞（CD20 阴性）的 90 倍（p<0.0001）。免疫反应性超过 75%。用 Cu-DOTA-利妥昔单抗进行的 PET/CT 成像在肿瘤中特异性观察到。肿瘤的放射性明显高于其他器官，肿瘤摄取与 CD20 表达有关。Cu-DOTA-利妥昔单抗给药的预测人体剂量被测量为有效剂量（1.07E-02 mSv/MBq）。在肿瘤区域，Ac-DOTA-利妥昔单抗（14 Sv/MBq）的当量剂量（14 Sv/MBq）明显高于 Cu-DOTA-利妥昔单抗（0.19 Sv/MBq）（p<0.01）。
可以通过铜-DOTA-利妥昔单抗的蒙特卡罗模拟来估算 Ac-DOTA-利妥昔单抗的肿瘤剂量学。可以将 Ac-DOTA-利妥昔单抗用于淋巴瘤的靶向α治疗。
