Gold Nanoparticle Contrast Agents: MicroCT of Colon Cancer

金纳米粒子造影剂：结肠癌的 MicroCT

• 批准号: 7225829
• 负责人: James F Hainfeld
• 金额: $ 44.33万
• 依托单位: NANOPROBES, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2008-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7225829
• 关键词: colon; colon neoplasms; gold; neoplasm /cancer

DESCRIPTION (provided by applicant): This proposal seeks to develop new contrast agents for in vivo microCT x-ray imaging based on non- toxic gold nanoparticles that would provide additional useful features over current agents including: a) longer imaging times, b) higher contrast, and c) targeted, tumor-specific imaging. Physically, gold is a better contrast element than iodine for both microCT and clinical CT because, for microCT the beam's energy spectrum can tailored to be above its 12-14-keV L-edge (e.g. 50 kVp), while for clinical CT it can be tuned to be above gold's 80.7-keV K-edge (e.g., 150 kVp with Cu filtration), thus optimizing the image contrast-to-noise ratio for both applications. Phase 1 work has succeeded in imaging 20 mu m blood vessels and obtaining vascular casts in live animals with this approach, never before achieved. Small, orthotopic colon tumors were also detected in vivo using gold nanoparticles. Phamacokinetics and toxicity were also shown to be acceptable. Gold-antibody conjugates were found to be specifically targeted to colon tumor cells in vitro. In Phase II, targeted molecular imaging will be extended to animals. Anti-CEA antibody-gold nanoparticles will be optimized to detect small human colon tumors in a mouse model by microCT. Additionally, vascular molecular markers in tumors will also be targeted. Further toxicity testing will be done and used to demonstrate or refine production of non-toxic gold contrast agents. R&D effort will result in products offered that other investigators can use. The benefits of this work will be: a) the enabling of high resolution in vivo CT contrasted detection and study of colon tumors and their vasculature, b) the introduction of contrast agent products that will then be available to other researchers using microCTs that will enable vascular and targeted imaging, c) to address and overcome the remaining obstacles to make these agents acceptable for human use. If successful, this effort will produce superior blood pool agents and the first targeted CT contrast agent, goals that have been difficult to achieve by other approaches.

描述（由申请人提供）：该提案旨在开发基于无毒金纳米颗粒的用于体内microCT X射线成像的新造影剂，其将提供优于当前试剂的额外有用特征，包括：a）更长的成像时间，B）更高的对比度，和c）靶向的肿瘤特异性成像。在物理上，对于微型CT和临床CT两者，金是比碘更好的对比元素，因为对于微型CT，射束的能谱可以被定制为高于其12-14-keV的L边缘（例如，50 kVp），而对于临床CT，其可以被调谐为高于金的80.7-keV的K边缘（例如，150 kVp（带Cu滤波），从而优化了两种应用的图像对比度噪声比。第一阶段的工作已经成功地成像20 μ m的血管，并获得血管铸型在活的动物与这种方法，从来没有实现。小的原位结肠肿瘤也在体内使用金纳米颗粒检测。药物代谢和毒性也被证明是可接受的。金-抗体偶联物被发现在体外特异性靶向结肠肿瘤细胞。在第二阶段，靶向分子成像将扩展到动物。抗CEA抗体-金纳米颗粒将被优化，以通过microCT检测小鼠模型中的小型人类结肠肿瘤。此外，肿瘤中的血管分子标志物也将被靶向。将进行进一步的毒性试验，并用于证明或改进无毒金造影剂的生产。研发工作将产生其他研究人员可以使用的产品。这项工作的好处将是：a）实现结肠肿瘤及其血管系统的高分辨率体内CT对比检测和研究，B）引入造影剂产品，然后将可用于其他研究人员使用微CT，这将使血管和靶向成像，c）解决和克服剩余的障碍，使这些药物可接受的人类使用。如果成功的话，这一努力将产生上级血池剂和第一个靶向CT造影剂，这是其他方法难以实现的目标。