Targeting of a head and neck squamous cell carcinoma xenograft model using the chimeric monoclonal antibody U36 radioiodinated with a closo-dodecaborate-containing linker

Targeting of a head and neck squamous cell carcinoma xenograft model using the chimeric monoclonal antibody U36 radioiodinated with a closo-dodecaborate-containing linker
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DOI:
10.1080/00016480410017891
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发表时间:
2004-11-01
影响因子:
1.4
通讯作者:
Anniko, M
Anniko, M
中科院分区:
医学4区
文献类型:
--
作者:
Cheng, JP;Persson, M;Anniko, M

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高级别头颈部鳞状细胞癌(HNSCC)手术后局部复发和远处转移的高发生率需要使用辅助全身治疗。放射免疫靶向可能是一种可能的治疗方式在这种情况下。I-131的核特性使其成为治疗微小残留病和小转移瘤的合适同位素,但常规放射性碘标记的细胞滞留性差,其放射性核素在甲状腺中积累。我们试图克服这些问题,通过使用closo-dodecaborate衍生物的附件的radioiodiation.Material和Methods-我们调查的可行性,在体内靶向SCC 25 HNSCC异种移植物,使用苄基异硫氰酸衍生物的closo-dodecaborate(DABI)作为放射性碘接头和嵌合抗CD 44 v6抗体U36。I-125被用于biodistribution studies.Results-The use of DABI enables tumor targeting and reduced the radioactivity uptake of the thyroid. Conclusion-Tumor localization of DABI-labeled U36 is similar to its para-iodobenzoate-labeled counterpart,推测是由于肿瘤大小对靶向效率的强烈依赖。
Objective-High rates of local recurrence and distant metastases following surgery of high-grade head and neck squamous cell carcinoma (HNSCC) necessitate the use of adjuvant systemic treatment. Radioimmunotargeting might be a possible treatment modality in this case. The nuclear properties of I-131 make it a suitable isotope for treatment of minimal residual disease and small metastases, but the conventional radioiodine label has poor cellular retention and its radiocatabolites accumulate in the thyroid. We attempted to overcome these problems by using closo-dodecaborate derivatives for attachment of radioiodine.Material and Methods-We investigated the feasibility of targeting an SCC25 HNSCC xenograft in vivo using a benzylisothiocyanate derivative of closo-dodecaborate (DABI) as radioiodine linker and the chimeric anti-CD44v6 antibody U36. I-125 was used in biodistribution studies.Results-The use of DABI enabled tumor targeting and decreased the radioactivity uptake of the thyroid.Conclusion-Tumor localization of DABI-labeled U36 was similar to its para-iodobenzoate-labeled counterpart, presumably due to the strong dependence of targeting efficiency on tumor size.