Molecular Mammography of Her-2 Cancers using Gold Nanoparticles

使用金纳米粒子对 Her-2 癌症进行分子乳房 X 线摄影

• 批准号: 7845462
• 负责人: James F Hainfeld
• 金额: $ 29.54万
• 依托单位: NANOPROBES, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-26 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7845462
• 关键词: Accounting; Address; American; Antibodies; Biochemical; Biocompatible; Biopsy; Biopsy Specimen; Breast Cancer Detection; Cancer Patient; Clinical; Contrast Media; Detection; Early Diagnosis; Economics; Funding; Goals; Gold; Grant; Health Sciences; Image; Image-Guided Surgery; Investments; Magnetic Resonance Imaging; Malignant Neoplasms; Mammography; Methods; Molecular; Molecular Target; Monitor; Monoclonal Antibodies; Mutation Detection; Nanotechnology; Neoplasm Metastasis; Occupations; Outcome; Pain; Patients; Pharmaceutical Preparations; Phase; Positron-Emission Tomography; Proteins; Public Health; Recovery; Resolution; Roche brand of trastuzumab; Screening procedure; Secure; Small Business Innovation Research Grant; Technology; Time; Translations; United States National Institutes of Health; Work; cancer imaging; cancer type; clinical application; commercialization; improved; in vivo; irradiation; malignant breast neoplasm; molecular imaging; mouse model; nanoparticle; novel; outcome forecast; public health relevance; response; single photon emission computed tomography; tumor

DESCRIPTION (provided by applicant): This is a Competitive Revision application under Notice Number NOT-OD-09-058, with Notice Title "NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications". It is for the existing Phase II SBIR grant "Molecular Mammography of Her-2 Cancers using Gold Nanoparticles", R44CA124190. Cancer imaging is important for tumor detection, determination of prognosis and treatments, image guided surgery and irradiation, as well as for monitoring responses. Molecular imaging of specific targets could identify tumor types and enable selection of appropriate drugs. Although mammography is widely used and more rapid and with higher resolution compared to PET, SPECT, and MRI, there are currently no targeted mammography contrast agents. In this currently funded grant, we are developing molecular targeted agents for mammography and CT by a nanotechnology approach using gold nanoparticle conjugates for imaging breast cancers. Her 2/neu protein is being targeted by use of antibodies attached to biocompatible gold nanoparticles using a mouse model. This would then be useful for non-invasive in vivo detection of this mutation which occurs in about 30% of breast cancers that could then be beneficially treated with the monoclonal antibody Herceptin. High resolution mammography and CT imaging would improve the limited sampling of biopsies and provide more thorough detection of even small tumors and metastases. If successful, this technology could be applied to other tumors for early detection and biochemical typing for more effective individualized treatments. Progress so far has demonstrated and quantified targeting to Her2-positive tumors compared to Her2- negative ones. Definitive detection of tumors smaller than currently possible has been shown using our approach, which has the potential to enable earlier and specific detection of breast cancers, and ultimately achieve better patient outcomes. However, a potential problem has become apparent during this work that might hinder clinical translation: the large gold nanoparticles (15 nm) used do not clear the body well, and their use might be difficult to justify in screening asymptomatic patients. Poor clearance would hinder FDA approval. Therefore, we propose in this Competitive Revision to develop gold nanoparticles that have good clearance. Overcoming this remaining obstacle would put in place a completed technology attractive to investors and clear the way for commercialization and clinical application. This work will address the American Recovery and Reinvestment Act (ARRA) of 2009 objectives by: 7 accelerating commercialization of the technology in order to achieve a significant benefit for cancer patients (by overcoming remaining obstacle) 7 creating new jobs 7 increasing economic efficiency by spurring technological advances in science and health 7 leveraging this one-time supplement by establishing critical strategic partnerships and/or securing third- party investments (i.e., non-federal funding) that will be necessary to achieve long-term commercialization goals (making the technology saleable to investors) PUBLIC HEALTH RELEVANCE: A novel method using nanotechnology will be developed for improved non-invasive imaging and detection of breast cancer types by mammography and CT. This should not only enable better early detection of smaller tumors and metastases without painful biopsies, but identify tumor types so that specific drugs for the type can be administered. Such a need exists to detect Her2 breast cancers, which account for about 30% of breast cancers, where the specific drug Herceptin(R) is available and improves survival.

描述（申请人提供）：这是一项竞争性修订申请，该申请是根据通知号而不是-OD-09-058，其通知标题“ NIH宣布恢复ACT资金可用于有竞争力的修订申请”。它是针对现有的II期SBIR赠款“使用金纳米颗粒的HER-2癌的分子乳房X线摄影”，R44CA124190。 癌症成像对于肿瘤检测，预后和治疗，图像引导手术和照射以及监测反应很重要。特定靶标的分子成像可以鉴定肿瘤类型，并可以选择适当的药物。尽管与PET，SPECT和MRI相比，乳房X线摄影被广泛使用，更快，分辨率更高，但目前尚无靶向乳腺X线摄影对比剂。在当前资助的赠款中，我们正在使用纳米技术方法使用金纳米颗粒偶联物来成像乳腺癌的纳米技术方法，以开发用于乳房X线摄影和CT的分子靶向剂。她的2/NEU蛋白是通过使用小鼠模型使用与生物相容性金纳米颗粒相连的抗体来靶向的。然后，这对于在大约30％的乳腺癌中发生的非侵入性体内检测将是有用的，该突变发生在大约30％的乳腺癌中，然后可以通过单克隆抗体赫赛汀进行有益地治疗。高分辨率乳房摄影和CT成像将改善活检的有限抽样，并更彻底地检测到小肿瘤和转移酶。如果成功的话，该技术可以应用于其他肿瘤，以进行早期检测和生化分型，以进行更有效的个性化处理。 到目前为止，与HER2-阴性肿瘤相比，迄今为止的进展已证明并量化了针对HER2阳性肿瘤的靶向。使用我们的方法表明，已经显示出比当前可能更小的肿瘤的确定检测，这有可能使乳腺癌的早期和特定检测，并最终取得更好的患者结局。 但是，在这项工作中，潜在的问题可能会阻碍临床翻译：所使用的大金纳米颗粒（15 nm）不能很好地清除身体，并且它们的使用可能很难证明在筛查无症状患者中。较差的许可将阻碍FDA的批准。因此，我们建议在这种竞争性修订中开发具有良好许可的金纳米颗粒。克服剩余的障碍将带来对投资者有吸引力的完整技术，并为商业化和临床应用扫清道路。这项工作将解决2009年目标的《美国恢复和再投资法》（ARRA）：7加速技术的商业化，以便为癌症患者获得重大利益（通过克服剩余的障碍）7创造新的工作7通过促进技术进步来提高经济效率，从而促进科学和健康方面的技术进步7通过建立这一至关重要的策略竞争，而不是构建了良好的派对，而不是分解党的三分之二的派对，以否定党的竞争，而不是分解三分之二的派对，以下三分之二的派对，以下三分之二的派对，以下三分之二的派对，否定了三分之二的派对，以下三级策略，以下三项工作。实现长期商业化目标是必要的（使投资者可销售的技术） 公共卫生相关性：将开发一种使用纳米技术的新方法，用于改善乳腺摄影和CT对乳腺癌类型的检测。这不仅应该使得没有疼痛活检的较小肿瘤和转移的早期检测，而且还应识别肿瘤类型，以便可以施用该类型的特定药物。存在这种需求来检测HER2乳腺癌，该癌症约占乳腺癌的30％，其中特定的药物Herceptin（R）可用并提高了生存。