title: 186Re-labeled monoclonal antibody E48 immunoglobulin G-mediated therapy of human head and neck squamous cell carcinoma xenografts.
abstract: In our laboratory, a solid-phase synthesis of 186Re-mercaptoacetyltriglycine for reproducible and aseptic production of stable 186Re-monoclonal antibody conjugates was recently developed. Monoclonal antibody (MAb) E48 IgG, when labeled with 99mTc according to the same labeling procedure, was recently shown to be highly capable of detecting recurrent and metastatic disease in patients with head and neck squamous cell carcinoma. In the present study, MAb E48 was labeled with 186Re and tested for its capacity to eradicate established human head and neck squamous cell carcinoma xenografts growing s.c. in nude mice. Experimental groups received a single bolus injection of 200 [number of mice (n) = 6, number of tumors (t) = 11], 400 (n = 6, t = 11), 500 (n = 6, t = 12), or 600 (n = 5, t = 9) microCi 186Re-labeled MAb E48 IgG; control animals were given diluent (n = 4, t = 8). In the 200 microCi group, 5 of 11 tumors showed regression while the remaining tumors showed a decreased growth rate. In the other treatment groups, all tumors regressed. In all treatment groups, remissions were observed (no regrowth within 4 months after injection). The number of remissions in the 200, 400, 500, and 600 microCi group were 2 of 11 (18.2%), 3 of 11 (27.3%), 6 of 12 (50%), and 3 of 9 tumors (33.3%), respectively. In comparison with the median tumor volume doubling time of the controls, the tumor volume doubling time in the remaining tumors in the groups receiving 200, 400, 500, or 600 microCi was increased 5.5-, 7.8-, 8.7-, and 11.3-fold, respectively. Dosimetry was based on the biodistribution of 200 microCi 186Re-labeled MAb E48 IgG. In the group receiving 600 microCi, the absorbed cumulative radiation dose was 3432 cGy for tumor and 1356 cGy for blood. In other tissues, the accumulated dose was < 17% of the dose delivered to tumor. The whole-body dose was 11-fold lower than the dose delivered to tumor. Apparent toxicity was limited to weight loss, which did not exceed 12% and which returned to control levels within 2 weeks. No treatment-related deaths occurred. These data suggest radioimmunotherapy with 186Re-labeled MAb E48 IgG to be a feasible approach for the treatment of head and neck cancer.
authors.affiliation: Department of Otolaryngology and Head and Neck Surgery, Free University Hospital, De Boelelaan, Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Gerretsen
authors.forename: G W
authors.initials: GW
authors.lastname: Visser
authors.forename: M
authors.initials: M
authors.lastname: van Walsum
authors.forename: C J
authors.initials: CJ
authors.lastname: Meijer
authors.forename: G B
authors.initials: GB
authors.lastname: Snow
authors.forename: G A
authors.initials: GA
authors.lastname: van Dongen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy*; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D051379:Mice; D009368:Neoplasm Transplantation; D016499:Radioimmunotherapy; D011868:Radioisotopes / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D012211:Rhenium / Q000627:therapeutic use*; D014183:Transplantation, Heterologous
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D011868:Radioisotopes; D012211:Rhenium