Department of Otorhinolaryngology, Head and Neck Surgery, Dachau Medical Center, Krankenhausstrasse 15, 85221 Dachau, Germany.
Anticancer Res. 2011 Oct;31(10):3315-21.
A new promising approach to improve the outcome of head and neck squamous cell carcinoma (HNSCC) is the application of radio-labeled antibodies directed against tumor-associated antigens. Cytokeratin 8 (CK8), an intermediate filament forming protein, is shown to be de novo expressed in dysplastic lesions as well as in HNSCC. Therefore like the epithelial cell adhesion molecule CK8 seems to be a suitable anchor molecule for targeted radioimmunotherapy (RIT). The aim of this study was to investigate the biodistribution of a radio-labeled Cytokeratin 8-specific monoclonal antibody (mAb) in a SCID (severe combined immunodeficiency disease) mouse model.
The mAb against CK8 was labeled with (131)I and biodistribution was tested in established HNSCC xenografts in SCID mice. The biodistribution of the mAb in the tumor and different organs was determined with a gamma counter and was calculated as % injected dose/gram tissue.
Initially, after systemic administration of (131)I-anti CK8 monoclonal antibody high activity was seen in all the organs. Over time the general activity decreased, whereas activity accumulated in the tumor. This activity decayed compared to the other tissues with a two- to threefold prolonged radioactive half-life.
Specific antibody-antigen-binding is probably responsible for the prolonged radioactive half-life in the tumor and the resulting cumulative activity due to enrichment of the (131)I-anti CK8 mAb, so that Cytokeratin 8 seems to be a suitable anchor molecule for radioimmunotherapy in HNSCC.
提高头颈部鳞状细胞癌（HNSCC）治疗效果的一种新的有前途的方法是应用针对肿瘤相关抗原的放射性标记抗体。细胞角蛋白 8（CK8）是一种中间丝形成蛋白，在发育不良病变以及 HNSCC 中均有新表达。因此，CK8 似乎像上皮细胞黏附分子一样，是靶向放射免疫治疗（RIT）的合适锚定分子。本研究的目的是研究放射性标记的 CK8 特异性单克隆抗体（mAb）在 SCID（严重联合免疫缺陷疾病）小鼠模型中的生物分布。
用（131）I 标记针对 CK8 的 mAb，并在 SCID 小鼠中建立的 HNSCC 异种移植中测试其生物分布。使用伽马计数器测定 mAb 在肿瘤和不同器官中的生物分布，并计算为组织每克注射剂量的%。
最初，在全身性给予（131）I-抗 CK8 单克隆抗体后，所有器官中均可见高活性。随着时间的推移，总体活性下降，而活性在肿瘤中积累。与其他组织相比，放射性半衰期延长了两到三倍，因此活性下降。
特异性抗体-抗原结合可能是导致肿瘤中放射性半衰期延长和由此导致的累积活性的原因，因为（131）I-抗 CK8 mAb 被富集，因此 CK8 似乎是 HNSCC 放射免疫治疗的合适锚定分子。
