Nestor M, Persson M, van Dongen G A M S, Jensen H J, Lundqvist H, Anniko M, Tolmachev V
Unit of Otolaryngology and Head & Neck Surgery, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
Eur J Nucl Med Mol Imaging. 2005 Nov;32(11):1296-304. doi: 10.1007/s00259-005-1848-2. Epub 2005 Jul 19.
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.
本研究旨在分析碘化嵌合单克隆抗体（cMAb）U36作为一种偶联物的特性，以选择性靶向并根除头颈部鳞状细胞癌（HNSCC）。
通过连接子N-琥珀酰亚胺基4-（三甲基锡基）苯甲酸酯（SPMB）用211At标记cMAb U36。对该偶联物的质量进行了广泛的结合和内化能力评估，并与125I-SPMB-cMAb U36进行比较。在两种体外生长试验中评估了碘化偶联物的细胞毒性，并与131I标记的cMAb U36（直接标记）进行比较。
211At-cMAb U36与125I-cMAb U36之间的比较表明标记产物具有最佳功能能力。免疫反应性和亲和力测定显示高免疫反应分数（>93%），且碘化抗体与碘化抗体之间的亲和力良好。对于两种偶联物，均可证明其与HNSCC细胞的特异性结合以及一定程度的内化。碘化偶联物的保留率略低于碘化偶联物，但仍适用于治疗用途（22小时时为31±2%对42.6±1.0%），表明抗体碘化对其无不良影响。细胞毒性研究表明，211At-cMAb U36具有剂量依赖性和抗原特异性细胞毒性，在每个细胞50次衰变时细胞存活率约为10%。131I标记的偶联物效率不高，在每个细胞55次衰变时存活细胞分数约为50%。
这些结果表明，211At-cMAb U36可能是未来体内根除HNSCC微转移的有前景的候选物。
