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（由申请人提供）：这是一份竞争性修订申请，通知编号为NOT-OD-09-058，通知标题为“NIH宣布恢复法案资金可用于竞争性修订申请”。这是现有的第二阶段SBIR资助“使用金纳米颗粒的Her-2癌症分子乳腺X线摄影”，R44 CA 124190。 癌症成像对于肿瘤检测、预后和治疗的确定、图像引导的手术和放射以及监测反应是重要的。特定靶点的分子成像可以识别肿瘤类型，并选择合适的药物。尽管乳房X线摄影术被广泛使用，并且与PET、SPECT和MRI相比更快速且具有更高的分辨率，但目前没有靶向乳房X线摄影术造影剂。在这项目前资助的赠款中，我们正在通过纳米技术方法开发用于乳腺X射线摄影和CT的分子靶向药物，该方法使用金纳米颗粒缀合物对乳腺癌进行成像。使用小鼠模型，使用附着在生物相容性金纳米颗粒上的抗体来靶向她的2/neu蛋白。然后，这将用于该突变的非侵入性体内检测，该突变发生在约30%的乳腺癌中，然后可以用单克隆抗体赫赛汀有益地治疗。高分辨率乳房X线摄影和CT成像将改善活检的有限采样，并提供更彻底的检测，即使是小肿瘤和转移。如果成功，这项技术可以应用于其他肿瘤的早期检测和生化分型，以获得更有效的个性化治疗。 迄今为止的进展已经证明并量化了与Her 2阴性肿瘤相比，Her 2阳性肿瘤的靶向。使用我们的方法已经显示出比目前可能的更小的肿瘤的连续检测，这有可能实现乳腺癌的早期和特异性检测，并最终实现更好的患者结局。 然而，在这项工作中，一个可能阻碍临床转化的潜在问题变得明显：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难以证明在筛查无症状患者中的合理性。不良的许可将阻碍FDA的批准。因此，我们在本竞争性修订版中建议开发具有良好清除率的金纳米颗粒。克服这一剩余的障碍将使一项对投资者有吸引力的完整技术到位，并为商业化和临床应用扫清道路。这项工作将通过以下方式实现2009年《美国复苏和再投资法案》的目标：7.加速该技术的商业化，以便为癌症患者带来重大利益（通过克服剩余的障碍）7创造新的就业机会7通过刺激科学和卫生领域的技术进步7提高经济效率7利用这一点-通过建立关键的战略伙伴关系和/或获得第三方投资（即，非联邦资金），这将是必要的，以实现长期的商业化目标（使技术出售给投资者） 公共卫生相关性：将开发一种使用纳米技术的新方法，用于改进非侵入性成像和通过乳房X线摄影和CT检测乳腺癌类型。这不仅可以更好地早期检测较小的肿瘤和转移，而无需进行痛苦的活检，而且可以识别肿瘤类型，以便可以针对该类型给予特定药物。存在检测Her 2乳腺癌的这种需求，Her 2乳腺癌占乳腺癌的约30%，其中特异性药物Herceptin（R）可用并提高存活率。