astatine and Head-and-Neck-Neoplasms

In advanced head and neck squamous cell carcinoma (HNSCC), there is a need for an adjuvant treatment. We aim to evaluate the biodistribution and therapeutic effect of radioimmunotherapy using the alpha emitting, astatine-211-labeled, chimeric monoclonal antibody U36 (U36) on the HNSCC cell line UT-SCC7 in vivo.. Xenograft tumors were inoculated subcutaneously in nude mice. Astatine-211-labeled U36 was injected intravenously with or without blocking of target with nonlabeled U36.. In the biodistribution experiments, radioactivity was measured in tumors and various organs at set time points. In the therapeutic experiments, two groups (with or without blocking) received therapy, and the tumor growth was compared with that of controls. In addition, one group received nonlabeled U36 only.. The biodistribution experiments demonstrated that astatine-211-labeled U36 could target UT-SCC7 xenografts in nude mice. With time, uptake increased in tumors and decreased in normal organs. Nonlabeled U36 did not influence tumor growth. In the two therapy groups, 18 of 20 tumors responded to therapy by decreasing or stabilizing their volumes. Significant difference was seen between the treated groups and the controls (P < .05).. The study illustrates the specific binding of astatine-211-labeled U36 to HNSCC and suggests radioimmunotherapy with the alpha emitting radionuclide to be a useful treatment modality.

Topics: Animals; Antibodies, Monoclonal; Astatine; Carcinoma, Squamous Cell; Cell Growth Processes; Cell Line, Tumor; Cell Movement; Chimerin Proteins; Disease Models, Animal; Head and Neck Neoplasms; Mice; Mice, Nude; Radioimmunotherapy; Random Allocation; Staining and Labeling

The purpose of this study was to analyse the properties of the astatinated chimeric MAb (cMAb) U36 as a conjugate to selectively target and eradicate head and neck squamous cell carcinoma (HNSCC).. cMAb U36 was labelled with 211At via the linker N-succinimidyl 4-(trimethylstannyl)benzoate (SPMB). The quality of the conjugate was extensively evaluated for binding and internalisation capacity, and compared with 125I-SPMB-cMAb U36. The cellular toxicity of the astatinated conjugate was assessed in two types of in vitro growth assay and compared with 131I-labelled cMAb U36 (directly labelled).. Comparisons between 211At-cMAb U36 and 125I-cMAb U36 demonstrated an optimal functional capacity of the labelled products. Immunoreactivity and affinity assays showed high immunoreactive fractions (>93%), and an affinity in good agreement between the astatinated and iodinated antibodies. For both conjugates, specific binding to HNSCC cells could be demonstrated, as well as some internalisation. Retention of the astatinated conjugate was just slightly lower than for the iodinated conjugate and still reasonable for therapeutic use (31+/-2% vs 42.6+/-1.0% at 22 h), demonstrating no adverse effects from astatination of the antibody. Studies on cellular toxicity demonstrated a dose-dependent and antigen-specific cellular toxicity for 211At-cMAb U36, with about 10% cell survival at 50 decays per cell. The 131I-labelled conjugate was not as efficient, with a surviving cell fraction of about 50% at 55 decays per cell.. These results indicate that 211At-cMAb U36 might be a promising future candidate for eradicating HNSCC micrometastases in vivo.

Topics: Antibodies, Monoclonal; Astatine; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Survival; Drug Evaluation, Preclinical; Feasibility Studies; Head and Neck Neoplasms; Humans; Radioimmunotherapy