Antibody-Guided In Vivo Imaging for Early Detection of Mammary Gland Tumors.
Antibody-Guided In Vivo Imaging for Early Detection of Mammary Gland Tumors.
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DOI：
10.1016/j.tranon.2016.05.001
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发表时间：
2016-08
影响因子：
5
通讯作者：
Dreau, Didier
中科院分区：
文献类型：
--
作者：
Moore, Laura Jeffords;Roy, Lopamudra Das;Zhou, Ru;Grover, Priyanka;Wu, Shu-ta;Curry, Jennifer M.;Dillon, Lloye M.;Puri, Priya M.;Yazdanifar, Mahboubeh;Puri, Rahul;Mukherjee, Pinku;Dreau, Didier
背景：使用靶点特异性成像技术早期检测转化细胞有很大的希望。我们已经开发出TAB 004，这是一种高度特异的单抗，可以在肿瘤形式的MUC1(TMUC1)中获得蛋白质序列。我们提供了在体外和体内基因工程小鼠中评估TAB 004的特异性和敏感性的数据。方法：将多瘤中T抗原小鼠与人MUC1Tg小鼠杂交，产生MMT小鼠。在MMT小鼠中，乳腺增生在6-10周龄时出现，12-14周龄时发展为导管原位癌，18-24周龄时发展为腺癌。其中大约40%的小鼠发生了肺部和其他器官的转移，其肿瘤进化过程与人类乳腺癌的发展过程非常相似。通过眼眶后注射标记吲哚青绿(TAB-ICG)的TAB 004(TAB-ICG)，通过体内成像监测了MMT小鼠(8-22周)的肿瘤进展情况。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：与体检相比，注射TAB-ICG后的活体成像可显著提早发现肿瘤。此外，在MMT小鼠体内注射TAB-ICG能够检测到肺转移，同时避免识别正常的上皮细胞。结论：这些数据突出了TAB 004抗体在区分正常形式和肿瘤形式的MUC1方面的特异性和敏感性，以及它作为靶向显像剂用于早期发现、肿瘤监测反应以及靶向给药的潜在临床应用。
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.
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影响因子：
8.4
作者：
McVeigh, Terri Patricia;Hughes, Lauren M.;Kerin, Michael J.
通讯作者：
Kerin, Michael J.
影响因子：
254.7
作者：
DeSantis, Carol;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
1.1
作者：
Moshina, Nataliia;Ursin, Giske;Hofvind, Solveig
通讯作者：
Hofvind, Solveig
影响因子：
3.8
作者：
Debald, Manuel;Abramian, Alina;Schild, Hans H.
通讯作者：
Schild, Hans H.
影响因子：
5.3
作者：
GUY, CT;CARDIFF, RD;MULLER, WJ
通讯作者：
MULLER, WJ