Multiparametric monitoring of tumor response to chemotherapy by noninvasive imaging.
Multiparametric monitoring of tumor response to chemotherapy by noninvasive imaging.
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DOI：
10.1158/0008-5472.can-08-2001
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发表时间：
2009-02-01
期刊：
影响因子：
11.2
通讯作者：
Moore A
中科院分区：
文献类型：
--
作者：
Medarova Z;Rashkovetsky L;Pantazopoulos P;Moore A
随着癌症个体化治疗概念的出现，开发无创评估治疗结果的方法变得至关重要。考虑到这一点，我们设计了一种新的方法，在临床前乳腺癌模型中全面评价对已建立的药物阿霉素化疗的反应。这种方法不仅提供了关于肿瘤大小变化的信息，而且还提供了关于靶抗原表达的信息。我们的策略依赖于肿瘤特异性造影剂（MN-EPPT）靶向糖基化不足的MUC-1（uMUC-1）肿瘤抗原，发现超过90%的乳腺癌和化疗反应的预测。MN-EPPT由用于磁共振成像的超顺磁性氧化铁纳米颗粒（MN）组成，用Cy5.5染料修饰（用于近红外荧光光学成像，NIRF），并与肽（EPPT）缀合，特异性识别uMUC-1。在体内，用阿霉素治疗原位人乳腺癌小鼠导致肿瘤质量减少，并导致uMUC-1下调。MN-EPPT的肿瘤特异性积累允许通过非侵入性成像评估肿瘤体积的变化。此外，在注射MN-EPPT的小鼠中，在用多柔比星治疗后肿瘤Δ-T2显著减少，表明MN-EPPT的累积较低，并反映了uMUC-1的表达减少。通过这些研究，我们证明了磁共振成像在乳腺肿瘤化疗反应的多参数表征中的实用性。这种方法有可能显着提高我们的能力，更好地指导分子靶向个性化治疗方案的发展，因为它允许在分子尺度上监测治疗。
With the emerging concept of individualized cancer therapy, it becomes crucial to develop methods for the noninvasive assessment of treatment outcome. With this in mind, we designed a novel approach for the comprehensive evaluation of response to chemotherapy with the established agent doxorubicin in a pre-clinical breast cancer model. This approach delivers information not only about change in tumor size but also about target antigen expression. Our strategy relies on a tumor-specific contrast agent (MN-EPPT) targeting the underglycosylated MUC-1 (uMUC-1) tumor antigen, found on over 90% of breast cancers and predictive of chemotherapeutic response. MN-EPPT consists of superparamagnetic iron oxide nanoparticles (MN) for magnetic resonance imaging, modified with Cy5.5 dye (for near-infrared fluorescence optical imaging, NIRF), and conjugated to peptides (EPPT), specifically recognizing uMUC-1. In vivo, treatment of mice bearing orthotopic human breast carcinomas with doxorubicin led to a reduction in tumor mass and resulted in downregulation of uMUC-1. The tumor-specific accumulation of MN-EPPT allowed the assessment of change in tumor volume by noninvasive imaging. Furthermore, in mice injected with MN-EPPT, tumor delta-T2 was significantly reduced after treatment with doxorubicin, indicating a lower accumulation of MN-EPPT and reflecting the reduced expression of uMUC-1. With these studies, we have demonstrated the utility of magnetic resonance imaging for the multiparametric characterization of breast tumor response to chemotherapy. This approach has the potential of significantly advancing our ability to better direct the development of molecularly-targeted individualized therapy protocols, since it permits the monitoring of therapy on a molecular scale.