Multicolor in vivo targeted imaging to guide real-time surgery of HER2-positive micrometastases in a two-tumor coincident model of ovarian cancer.
Multicolor in vivo targeted imaging to guide real-time surgery of HER2-positive micrometastases in a two-tumor coincident model of ovarian cancer.
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DOI：
10.1111/j.1349-7006.2009.01133.x
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发表时间：
2009-06
期刊：
影响因子：
5.7
通讯作者：
Kobayashi H
中科院分区：
文献类型：
--
作者：
Longmire M;Kosaka N;Ogawa M;Choyke PL;Kobayashi H
肿瘤分子成像的主要目标之一是准确识别和表征体内恶性组织。目前，分子成像依赖于靶向单个分子，该分子虽然在恶性肿瘤中过表达，但通常在正常组织中也以较低水平表达，从而导致肿瘤与背景比率（TBR）降低。一种提高癌症分子成像特异性的方法是采用多个探针，每个探针具有不同的荧光，以同时靶向几种表面抗原，以鉴定组织表达谱，而不是依赖于单个靶标的表达。分子成像的下一步将依赖于基于荧光的组织表征，因此将需要同时识别每个连接到不同靶向配体的几个光学探针的能力。我们通过向每只动物共注射两种不同的细胞系HER 2 +/RFP-SK 0 V3和HER 2-/RFP+ SHIN 3-RFP来创建新的“同时”卵巢癌小鼠模型，以建立其中动物同时具有可用于MRI成像的两种不同表型（HER 2 +/RFP+、HER 2-/RFP+）的肿瘤的疾病模型。用曲妥珠单抗-罗丹明绿色缀合物靶向SKOV 3细胞系的HER 2受体以产生绿色肿瘤植入物，而SHIN 3细胞的RFP质粒产生红色肿瘤植入物。我们证明，真实的体内多色成像是可行的，并且荧光特征可以用于指导疾病的手术切除。
One of the primary goals of oncologic molecular imaging is to accurately identify and characterize malignant tissues in vivo. Currently, molecular imaging relies on targeting a single molecule that while over-expressed in malignancy, is often also expressed at lower levels in normal tissue, resulting in reduced tumor to background ratios (TBR). One approach to increasing the specificity of molecular imaging in cancer is to employ multiple probes each with distinct fluorescence to target several surface antigens simultaneously, in order to identify tissue expression profiles, rather than relying on the expression of a single target. This next step forward in molecular imaging will rely on characterization of tissue based on fluorescence and therefore will require the ability to simultaneously identify several optical probes each attached to different targeting ligands. We created a novel “coincident” ovarian cancer mouse model by co-injecting each animal with two distinct cell lines, HER2+/RFP- SKOV3 and HER2-/RFP+ SHIN3-RFP, in order to establish a model of disease in which animals simultaneously bore tumors with two distinct phenotypes (HER2+/RFP+, HER2-/RFP+) which could be utilized for multicolor imaging. The HER2 receptor of the SKOV3 cell line was targeted with trastuzumab-rhodamine green conjugate to create green tumor implants, while the RFP plasmid of the SHIN3 cells created red tumor implants. We demonstrate that real time in vivo multicolor imaging is feasible and that fluorescence characteristics can then serve to guide the surgical removal of disease.
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