Multimodality in vivo Molecular Imaging for Prostate PDT

描述（由申请人提供）：前列腺癌是美国男性癌症死亡的第二大原因。本研究的长期目标是开发新型多模态分子成像技术，以改善前列腺癌的早期检测和图像引导治疗。在我们的机构，第二代光敏药物PC 4已经在Case综合癌症中心进行了光动力疗法（PDT）的评估。该药物目前正在进行临床前机制研究和两项I期临床试验，用于治疗皮肤癌，包括转移到皮肤的癌症。该研究小组的成员已经在动物模型中证明了PC 4-PDT治疗乳腺癌、卵巢癌和结肠癌的疗效。此外，合作研究者Nancy Oleinick博士发现PC 4-PDT在体外诱导前列腺癌细胞凋亡。我们现在正在将这种相对较新的治疗方式扩展到前列腺癌治疗。在R21阶段，我们将在小鼠模型中进行体内PDT治疗人前列腺癌异种移植物。将开发最先进的体内分子成像技术来评估PDT疗效。将开发各种成像模式的图像融合和配准以及定量图像分析方法，以将联合收割机功能生化图像与高分辨率解剖图像相结合。将确定肿瘤对PDT反应的早期基于图像的替代生物标志物，以预测治疗的成功。从这项研究中创建的非侵入性成像技术可以应用于其他癌症。它们可用于检测非常早期的癌症，优化治疗计划以进行个性化治疗，利用图像引导的微创治疗，并监测治疗效果。提出的成像策略具有很大的潜力，以提高公众健康，改善诊断和治疗癌症。

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.