Department of Life Science Engineering, Faculty of Modern Science and Technology, Nano Biotechnology Group, University of Tehran, Tehran, 1439957131, Iran.
Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), Tehran, 14155-1339, Iran.
J Cancer Res Clin Oncol. 2023 Aug;149(10):7779-7791. doi: 10.1007/s00432-023-04724-z. Epub 2023 Apr 8.
PURPOSE: Epidermal growth factor receptors (EGFRs) are overexpressed in a wide range of tumors and are attractive candidates to target in targeted therapies. This study aimed to introduce a novel radiolabeled compound, Lu-cetuximab-PAMAM G4, for the treatment of EGFR-expressing tumors. METHODS: In this study, the cetuximab mAb was bound to PAMAM G4 and labeled with Lu via DTPA-CHX chelator. The synthesized nanosystem was confirmed by different analyses such as DLS, FT-IR, TEM, and RT-LC. Cell viability of the radioimmunoconjugate was assessed over the EGFR-expressing cell line of SW480. The biodistribution of Lu-Cetuximab-PAMAMG4 was determined in different intervals after injection of the radiolabeled compound in normal and tumoral nude mice via scarification and SPECT images. RESULTS: The average size of PAMAM G4 and PAMAM-Cetuximab-DTPA-CHX nanoparticles were 2 and 70 nm, respectively. Lu-Cetuximab-PAMAMG4 was prepared with radiochemical purity of more than 98%. The survival rates of SW480 cells at 24, 48, and 72 h post-treatment withLu-Cetuximab-PAMAMG4 (500 nM) were 18%, 15%, and 14%, respectively. The biodistribution studies showed a significant accumulation of Lu-Cetuximab-PAMAM in the EGFR-expressing tumor. CONCLUSION: According to the results, this new agent can be considered as an efficient therapeutic complex for tumors expressing EGFR receptors.
目的：表皮生长因子受体（EGFR）在广泛的肿瘤中过表达，是靶向治疗的有吸引力的候选物。本研究旨在介绍一种新型放射性标记化合物 Lu-cetuximab-PAMAM G4，用于治疗 EGFR 表达的肿瘤。
方法：在这项研究中，将 cetuximab mAb 与 PAMAM G4 结合，并通过 DTPA-CHX 螯合剂标记 Lu。通过 DLS、FT-IR、TEM 和 RT-LC 等不同分析方法对合成的纳米系统进行了确认。通过放射性免疫偶联物对 EGFR 表达细胞系 SW480 的细胞活力进行了评估。通过划痕和 SPECT 图像，在正常和肿瘤裸鼠中注射放射性标记化合物后，在不同时间间隔内测定了 Lu-Cetuximab-PAMAMG4 的生物分布。
结果：PAMAM G4 和 PAMAM-Cetuximab-DTPA-CHX 纳米颗粒的平均粒径分别为 2nm 和 70nm。Lu-Cetuximab-PAMAMG4 的放射化学纯度大于 98%。用 Lu-Cetuximab-PAMAMG4（500nM）处理 SW480 细胞 24、48 和 72h 后，细胞存活率分别为 18%、15%和 14%。生物分布研究表明，Lu-Cetuximab-PAMAM 在表达 EGFR 受体的肿瘤中有明显的积聚。
结论：根据结果，这种新的药物可以被认为是一种治疗表达 EGFR 受体的肿瘤的有效治疗复合物。
J Cancer Res Clin Oncol. 2023-8
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