Otto Christina, Jensen Markus, Dietlein Markus, Fischer Thomas, Schmidt Matthias, Tawadros Samir, Börner Sarah Maria, Weber Sebastian Alfred, Spitz Rüdiger, Bloch Wilhelm, Berthold Frank, Schicha Harald, Schomäcker Klaus
Department of Nuclear Medicine, University of Cologne, Germany.
Nucl Med Commun. 2006 Feb;27(2):171-8. doi: 10.1097/01.mnm.0000194400.04820.7d.
To evaluate a novel strategy of immunolocalization of human neuroblastoma by targeting the neural cell adhesion molecule (NCAM), which is over-expressed on neuroblastoma.
NCAM expression on the cell surface of established neuroblastoma cells was shown by flow cytometry. A SCID mouse model using IMR5-75 neuroblastoma cells to induce subcutaneous tumour growth was established. 131I was used to label monoclonal NCAM specific ERIC1 antibodies generating the 131I-ERIC1 antibody, which showed a high affinity to NCAM also after labelling (KD=9 x 10(-8) mol . l(-1)).
Measurement of organ-specific radioactivity showed low organ-specific uptake (5.33%ID/g (percent of injected dose per gram of tissue) after 72 h), which continuously decreased over the 96 h investigation period, demonstrating clearance of radioactivity. In contrast, tumours accumulated radioactivity continuously up to a peak of 42.07%ID/g at the 96 h time point (31.07%ID/g at 72 h). This specific uptake could be blocked by application of unlabelled ERIC1 antibodies. Measurement of blood specific radioactivity revealed a characteristic clearance over the first 72 h. With 37 Gy, tumour-specific radioactivity reached therapeutic doses after 96 h.
These results indicate that 131I-labelled ERIC1 has the ability to probe NCAM-expressing tumour cells in vivo with high efficiency and is a promising reagent for the diagnosis and treatment of NCAM-positive human tumours, especially for neuroblastoma.
通过靶向神经母细胞瘤上过度表达的神经细胞黏附分子（NCAM），评估一种人神经母细胞瘤免疫定位的新策略。
通过流式细胞术显示已建立的神经母细胞瘤细胞表面的NCAM表达。建立了使用IMR5 - 75神经母细胞瘤细胞诱导皮下肿瘤生长的SCID小鼠模型。使用131I标记单克隆NCAM特异性ERIC1抗体，生成131I - ERIC1抗体，该抗体在标记后对NCAM也显示出高亲和力（KD = 9×10（-8）mol·l（-1））。
器官特异性放射性测量显示器官特异性摄取较低（72小时后为5.33%ID/g（每克组织注射剂量的百分比）），在96小时的研究期间持续下降，表明放射性物质被清除。相比之下，肿瘤持续积累放射性物质，在96小时时间点达到峰值42.07%ID/g（72小时时为31.07%ID/g）。这种特异性摄取可通过应用未标记的ERIC1抗体来阻断。血液特异性放射性测量显示在最初72小时内有特征性清除。给予37 Gy后，96小时后肿瘤特异性放射性达到治疗剂量。
这些结果表明，131I标记的ERIC1能够在体内高效探测表达NCAM的肿瘤细胞，是一种用于诊断和治疗NCAM阳性人类肿瘤，尤其是神经母细胞瘤的有前景的试剂。
