BACKGROUND: Earlier detection of transformed cells using target-specific imaging techniques holds great promise. We have developed TAB 004, a monoclonal antibody highly specific to a protein sequence accessible in the tumor form of MUC1 (tMUC1). We present data assessing both the specificity and sensitivity of TAB 004 in vitro and in genetically engineered mice in vivo. METHODS: Polyoma Middle T Antigen mice were crossed to the human MUC1.Tg mice to generate MMT mice. In MMT mice, mammary gland hyperplasia is observed between 6 and 10 weeks of age that progresses to ductal carcinoma in situ by 12 to 14 weeks and adenocarcinoma by 18 to 24 weeks. Approximately 40% of these mice develop metastasis to the lung and other organs with a tumor evolution that closely mimics human breast cancer progression. Tumor progression was monitored in MMT mice (from ages 8 to 22 weeks) by in vivo imaging following retro-orbital injections of the TAB 004 conjugated to indocyanine green (TAB-ICG). At euthanasia, mammary gland tumors and normal epithelial tissues were collected for further analyses. RESULTS: In vivo imaging following TAB-ICG injection permitted significantly earlier detection of tumors compared with physical examination. Furthermore, TAB-ICG administration in MMT mice enabled the detection of lung metastases while sparing recognition of normal epithelia. CONCLUSIONS: The data highlight the specificity and the sensitivity of the TAB 004 antibody in differentiating normal versus tumor form of MUC1 and its utility as a targeted imaging agent for early detection, tumor monitoring response, as well as potential clinical use for targeted drug delivery.

背景：使用靶标特异性成像技术对转化细胞进行早期检测具有广阔的前景。我们已经开发出TAB 004，这是一种单克隆抗体，对在MUC1（tMUC1）肿瘤形式中可及的蛋白质序列具有高度特异性。我们目前评估TAB 004在体外和基因工程小鼠体内的特异性和敏感性的数据。方法：将Polyoma Middle T Antigen小鼠与人类MUC1.Tg小鼠杂交，以生成MMT小鼠。在MMT小鼠中，观察到6至10周龄的乳腺增生会发展为原位导管癌在12至14周内切除腺癌，在18至24周内切除腺癌。这些小鼠中约有40％发生向肺和其他器官的转移，其肿瘤演变与人类乳腺癌的发展极为相似。在眼眶后注射偶联吲哚花青绿的TAB 004（TAB-ICG）后，通过体内成像监测MMT小鼠（8至22周龄）的肿瘤进展。在安乐死时，收集乳腺肿瘤和正常上皮组织进行进一步分析。结果：与物理检查相比，TAB-ICG注射后的体内成像可显着更早地发现肿瘤。此外，在MMT小鼠中使用TAB-ICG可以检测到肺转移，同时又不影响正常的上皮细胞。结论：数据突出了TAB 004抗体在区分正常形式与肿瘤形式的MUC1上的特异性和敏感性，以及其作为靶向成像剂的早期检测，肿瘤监测反应以及靶向药物递送的潜在临床用途。