The Siteman Center of Cancer Nanotechnology Excellence *

描述（由申请人提供）：在过去的三十年中，乳腺癌、结肠癌和前列腺癌的早期检测取得了许多值得注意的进展，改善了治疗方法，在某些情况下，改善了结果。然而，在这段时间内，癌症的发病率继续增加，治疗（即手术、放疗和化疗）的发病率仍然不可接受，生存率仅略微提高。本提案的主题是应用一种新的顺磁定位对比“平台技术”，用于对肿瘤新血管上单独表达的分子表位进行敏感和特异性成像，并结合局部递送化疗药物到这些部位。3-整合素纳米颗粒有效靶向实体动物肿瘤和人类异种移植物，提供显著的MR t1加权对比和有效的抗肿瘤治疗。不幸的是，没有单一的血管生物特征在所有实体肿瘤中普遍存在。因此，肿瘤必须对更广泛的靶向药物进行无创检查，以便使用适当的单个或组合配体定向纳米颗粒进行个体化治疗。在这个项目中，我们将扩大这一成功的纳米技术平台的效用，以获得额外的早期生物特征，这些特征可以单独或同时用于最有效的诊断和化疗反应。同时，我们将开发无创成像软件和硬件，以利用全氟碳纳米颗粒为19F磁共振光谱、19F成像和1H/19F混合成像提供的独特机会。使用19F光谱和成像不仅可以为目标纳米颗粒应用增加定量和光谱维度，而且19F成像还可以消除对图像的基线数字减法的需要，这既耗时又容易出错。交错1H/19F混合成像将最大限度地减少运动伪影，消除图像配准问题，确认对比度识别并缩短患者扫描时间。

DESCRIPTION (provided by the applicant): Over the last thirty years many noteworthy advances in the early detection of breast, colon, and prostate cancer have improved treatment and, in some instances, improved outcomes. Yet during this timeframe, the incidence of cancer continued to increase, morbidity from treatments (i.e., surgery, radiation and chemotherapy) remained unacceptable, and survival only improved marginally. The subject of this proposal is the application of a novel paramagnetic site-targeted contrast "platform technology" for sensitive and specific imaging of molecular epitopes expressed on tumor neovasculature alone and in combination with the local delivery of chemotherapeutic agents to these sites. av¿3-integrin nanoparticles effectively target solid animal tumors and human xenografts to provide marked MR T1-weighted contrast and potent anti-tumor therapy. Unfortunately, no single vascular biosignature is ubiquitous across all solid tumors. Therefore, tumors must be noninvasively interrogated against a broader panel of targeted agents in order to individualize therapy with the appropriate single or combination of ligand directed nanoparticles. This program, we will expand utility of this successful nanotechnology platform to additional early biosignatures that may be targeted alone or simultaneously for the most effective diagnostic and chemotherapeutic response. In parallel, we will develop noninvasive imaging software and hardware to exploit the unique opportunity presented by perfluorocarbon nanoparticles for 19F MR spectroscopy, 19F imaging, and 1H/19F hybrid imaging. The use of 19F spectroscopy and imaging will not only add quantitative and spectral dimensionality to targeted nanoparticle applications, but 19F imaging can also eliminate the need for baseline digital subtraction of images, which is time-consuming and prone to error. Interleaved 1H/19F hybrid imaging will minimize motion artifacts, eliminate image registration issues, confirm contrast identification and shorten patient scanning times.