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方面的许多值得注意的进展改善了治疗，并且在某些情况下改善了结局。 然而，在这段时间内，癌症的发病率继续增加，治疗的发病率（即，手术、放疗和化疗）仍然是不可接受的，生存率仅略有提高。 本提案的主题是应用一种新的顺磁性靶向位点的对比“平台技术”，用于对肿瘤新生血管系统上表达的分子表位单独进行敏感和特异性成像，以及与局部递送化疗剂到这些位点相结合。 阿伏β-整联蛋白纳米颗粒有效地靶向实体动物肿瘤和人异种移植物，以提供显著的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瘤中普遍存在。 因此，肿瘤必须针对更广泛的靶向药物进行非侵入性询问，以便使用适当的配体导向纳米颗粒的单一或组合进行个体化治疗。 在这个项目中，我们将把这个成功的纳米技术平台的效用扩展到额外的早期生物特征，这些生物特征可以单独或同时被靶向，以获得最有效的诊断和化疗反应。同时，我们将开发非侵入性成像软件和硬件，以利用全氟化碳纳米颗粒为19 F MR光谱，19 F成像和1H/19 F混合成像提供的独特机会。 使用19 F光谱和成像不仅可以为靶向纳米颗粒应用增加定量和光谱维度，而且19 F成像还可以消除对图像基线数字减法的需要，这是耗时且容易出错的。 交错1H/19 F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.