Colapinto E V, Lee Y S, Humphrey P A, Zalutsky M R, Friedman H S, Bullard D E, Bigner D D
Department of Pathology, Preuss Laboratory for Brain Tumor Research, Duke University Medical Center, Durham, North Carolina 27710.
Br J Neurosurg. 1988;2(2):179-91. doi: 10.3109/02688698808992668.
The localisation of the radioiodinated Fab fragment of monoclonal antibody (Mab) 81C6, reactive with a glioma-associated extracellular matrix antigen, was studied in athymic mice bearing subcutaneous and intracranial xenografts of D-54 MG glioma cells. In vitro 81C6 Fab showed a marked loss of immunoreactivity and affinity for antigen compared to intact Mab 81C6. In vivo, the plasma half-life of 81C6 Fab was 7.0 hours compared to 2.1 days for 81C6. 81C6 Fab levels in tumours peaked at 2.6-3.8% injected dose/g in 2-6 h; Mab 81C6 reached 33.9% dose/g at 48 h. Localisation indices and tumour:tissue ratios were superior for Mab 81C6. Estimated radiation doses to tumour and normal tissues were lower for 131I-81C6 Fab than 131I-81C6. To realise the theoretical benefits of fragments as localising agents, Fab fragments of higher immunoreactivity and affinity, or bivalent F(ab')2 fragments are required.
研究了与神经胶质瘤相关细胞外基质抗原发生反应的单克隆抗体（Mab）81C6的放射性碘化Fab片段在携带D-54 MG神经胶质瘤细胞皮下和颅内异种移植瘤的无胸腺小鼠中的定位情况。与完整的Mab 81C6相比，体外实验中81C6 Fab对抗原的免疫反应性和亲和力显著丧失。在体内，81C6 Fab的血浆半衰期为7.0小时，而81C6为2.1天。肿瘤中的81C6 Fab水平在2至6小时内达到峰值，为注射剂量/克的2.6 - 3.8%；Mab 81C6在48小时时达到33.9%剂量/克。Mab 81C6的定位指数和肿瘤与组织的比率更高。131I - 81C6 Fab对肿瘤和正常组织的估计辐射剂量低于131I - 81C6。为了实现片段作为定位剂的理论优势，需要具有更高免疫反应性和亲和力的Fab片段或二价F(ab')2片段。
