Efficacy of nimotuzumab (hR3) conjugated with 131I or 90Y in laryngeal carcinoma xenograft mouse model

• Published in: International journal of radiation biology 2021-05, Vol.97 (5), p.704-713
• Main Authors: Nguyen, Thi-Thu, Ho, Anh-Son, Nguyen, Thi-Khanh-Giang, Nguyen, Thi-Ngoc, Bui, Van-Cuong, Nguyen, Thanh-Binh, Dang, Ho-Hong-Quang, Nguyen, Dang-Khoa, Nguyen, Thanh-Nhan, Nguyen, Linh-Toan
• Format: Article
• Language: English
• Subjects: HEp-2 xenograft; I-nimotuzumab; Larynx Cancer; Radioimmunotherapy; Y-DOTA-nimotuzumab
• ISSN: 0955-3002; 1362-3095; 1362-3095
• DOI: 10.1080/09553002.2021.1889703

The humanized monoclonal antibody hR3, both alone and in combination with other chemotherapeutic agents and radiotherapy, can be used to treat head and neck cancers. Substantial progress has been made in the development of targeted radioimmunotherapy using iodine-131 ( 131 I) and yttrium-90 ( 90 Y) radioisotopes in recent years. In the present study, we examined the efficacy of hR3 conjugated with 131 I or 90 Y to inhibit tumor growth in a laryngeal carcinoma xenograft tumor model. hR3 was labeled with 131 I or 90 Y to generate the conjugates 131 I-hR3 or 90 Y-hR3. The conjugates were incubated with HEp-2 laryngeal carcinoma cells to evaluate binding capacity. The efficacy of the labeled hR3 conjugates to treat laryngeal cancer was also evaluated in nude mice inoculated with HEp-2 tumors. The purified radioimmunoconjugates with specific activities of 187-191 MBq/mg had radiochemical purity >98% and >80% immunoreactivity with HEp-2 cells. Mice with HEp-2 xenografts treated with 131 I-hR3 or 90 Y-hR3 showed reduced tumor volume and improved survival rates compared to the untreated control group and the group treated with unlabeled hR3. At equivalent doses, radioimmunotherapeutic hR3 labeled with 90 Y had increased tumor inhibition activity compared to hR3 labeled with 131 I. 131 I-hR3 and 90 Y-hR3 are promising targeted radiopharmaceuticals for treatment of head and neck cancers, especially laryngeal cancers.