Multimodality in vivo Molecular Imaging for Prostate PDT

描述(申请人提供)：前列腺癌是美国男性癌症死亡的第二大原因。这项研究的长期目标是开发新的多模式分子成像技术，以改进前列腺癌的早期发现和图像引导治疗。在我们机构，第二代光敏药物PC4已经在凯斯综合癌症中心接受了光动力疗法(PDT)的评估。该药物目前正在进行临床前机制研究和两个I期临床试验，用于治疗皮肤癌，包括转移到皮肤的癌症。这个研究小组的成员已经在动物模型中证明了PC4-PDT治疗乳腺癌、卵巢癌和结肠癌的有效性。此外，共同研究人员Nancy Oleinick博士发现，PC 4-PDT在体外可以诱导前列腺癌细胞凋亡。我们现在正在将这一相对较新的治疗方式推广到前列腺癌治疗中。在R21期，我们将在小鼠模型上进行体内PDT治疗人前列腺癌异种移植。将开发最先进的体内分子成像技术来评估PDT的疗效。将发展多种成像方式的图像融合和配准以及定量图像分析方法，将功能生化图像与高分辨率解剖图像相结合。一个基于图像的肿瘤对PDT反应的早期替代生物标志物将被识别出来，以预测治疗的成功。这项研究将创造的非侵入性成像技术也可以应用于其他癌症。它们可以用来检测非常早期的癌症，优化个体化治疗的治疗计划，利用图像引导的微创治疗，并监测治疗效果。拟议的成像策略通过改进癌症的诊断和治疗，具有提高公众健康的巨大潜力。

DESCRIPTION (provided by applicant): Prostate cancer is the second leading cause of cancer mortality in American men. The long-term objective of this research is to develop novel multimodality molecular imaging techniques for improved early detection and image-guided therapy for prostate cancer. At our institution, a second generation photosensitizing drug PC 4 has been evaluated for photodynamic therapy (PDT) at the Case Comprehensive Cancer Center. This drug is currently undergoing pre-clinical mechanistic studies and two Phase I clinical trials for the treatment of dermal cancers, including cancers that are metastatic to the skin. Members of this investigating team have already proven the efficacy of PC 4-PDT for the treatment of breast, ovarian, and colon cancer in animal models. In addition, a co-investigator, Dr. Nancy Oleinick found that PC 4-PDT induces apoptosis in prostate cancer cells in vitro. We are now extending this relatively new treatment modality for prostate cancer therapy. In the R21 phase, we will perform in vivo PDT to treat human prostate cancer xenografts in a mouse model. State-of-the-art in vivo molecular imaging techniques will be developed to assess the PDT efficacy. Image fusion and registration of various imaging modalities and quantitative image analysis methods will be developed to combine functional biochemical images with high-resolution anatomic images. An early image-based surrogate biomarker of the tumor response to PDT will be identified to predict the success of the therapy. The noninvasive imaging techniques to be created from this study can be applied to other cancers. They can be used to detect very early cancers, optimize treatment planning for individualized therapy, utilize image-guided minimally invasive therapy, and monitor the therapeutic efficacy. The proposed imaging strategy has great potential to enhance public health by improving diagnosis and therapy of cancer.