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; 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非毒性金纳米颗粒的体内Microct X射线成像的新对比度，该成像将在当前药物中提供其他有用的特征，包括：a）更长的成像时间，b）较高的对比度以及c）靶向，c）靶向的，肿瘤特异性的成像。 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这两个应用的比率。第1阶段的工作已成功地成像20 Mu M血管并以这种方法获得了活动物中的血管铸造，从未实现过。还使用金纳米颗粒在体内检测到小的原位结肠肿瘤。 phamacokinetics和毒性也被证明是可以接受的。发现金抗体结合物在体外特异性针对结肠肿瘤细胞。在II期中，靶向分子成像将扩展到动物。将优化抗CEA抗体 - 金纳米颗粒，以通过MicroCT检测小鼠模型中的小人体结肠肿瘤。另外，肿瘤中的血管分子标记也将被靶向。将进行进一步的毒性测试，并用于证明或完善无毒金对比剂的产生。研发工作将导致其他调查人员可以使用的产品。这项工作的好处将是：a）实现对结肠肿瘤及其脉管造成的检测和研究的高分辨率，b）引入对比剂产品，然后将其用于其他研究人员使用，这些研究人员将使用启用血管和靶向成像的微观可用于处理和克服其他障碍，以使这些势不可挡的障碍能够使这些人使用，以使这些障碍能够使这些人使用。如果成功的话，这项工作将产生卓越的血液池代理和第一个有针对性的CT对比剂，而其他方法很难实现的目标。