Targeted Gold Nanoparticle-Bioconjugates for Imaging Breast Cancer

用于乳腺癌成像的靶向金纳米粒子生物结合物

• 批准号: 7450952
• 负责人: Raghuraman Kannan
• 金额: $ 14.95万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-20 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7450952
• 关键词: Adipose tissue; Affinity; Animal Model; Benign; Binding; Biology; Bombesin; Bombesin Receptor; Breast; Breast Cancer Cell; Breast Cancer Detection; Breast Cancer Early Detection; Breast Microcalcification; Caliber; California; Cancer Patient; Cancerous; Case Study; Cells; Clinical Trials; Computers; Condition; Contrast Media; Cutaneous; Death Rate; Detection; Development; Devices; Diagnosis; Diagnostic; Dose; Ductal; Early Diagnosis; Effectiveness; Enhancers; Evaluation; Exhibits; Funding; Gel; Generations; Goals; Gold; Human; Image; Image Enhancement; Implant; In Situ; In Vitro; Invasive; Investigation; Lead; Lesion; Libraries; Malignant - descriptor; Malignant Neoplasms; Mammary Gland Parenchyma; Mammary Neoplasms; Mammography; Measurement; Mediating; Medicine; Methods; Modality; Nanotechnology; Noise; Outcome; Patients; Peptides; Phase; Physical Examination; Population; Property; Protocols documentation; Radiation; Rate; Research; Resolution; Roentgen Rays; SCID Mice; Screening for cancer; Screening procedure; Self-Examination; Sepharose; Shapes; Site; Specificity; Staging; Survival Rate; Time; Tissues; Tomography, Computed, Scanners; Transmission Electron Microscopy; Tumor Specific Peptide; Universities; Woman; Work; X-Ray Computed Tomography; Xenograft procedure; analog; attenuation; base; breast cancer diagnosis; design; imaging probe; improved; in vivo; innovation; instrument; malignant breast neoplasm; molecular imaging; nanoparticle; nanoparticulate; nanoprobe; nanoscience; nanosized; particle; phantom model; retinal rods; simulation; size; tomography; tumor; tumor xenograft

DESCRIPTION (provided by applicant): This application describes the design of new gold nanoparticle based bioconjugates derived from synthetic bombesin (BBN) analogues to produce a new generation of site-directed computed tomography (CT) imaging agents for specific in vivo targeting of breast cancer cells. With the overarching goal of visualizing smaller lesion (and therefore earlier cancer detection) with better specificity, this work has the potential to increase the survival rate from breast cancer. Specifically, this application will explore whether targeted gold nanoparticles are capable of producing contrast enhancement (increased x-ray attenuation) so that CT can be used in precise and accurate functional/molecular imaging of breast cancer. Our specific aims for the proposed project are to: (i) Optimize synthetic protocols for targeted gold nanoparticles (AuNPs) conjugated to tumor specific peptide; (ii) Determine the concentrations of gold nanoparticles necessary to induce image contrast in CT imaging using anthropomorphic phantom models of the human breast, including malignant lesions; and (iii) Investigate the utility of Bombesin conjugated AuNPs as image enhancers in computer tomographic (CT) imaging of breast tumors in SCID mice implanted with human breast cancer xenografts. Phantom studies will be performed to evaluate the concentration of AuNP required to produce sufficient contrast to effectively detect breast cancer for a specifically designed Breast CT scanner. This assessment will be done with respect to radiation dose and the size of the lesion; it is anticipated that improved contrast will lead to earlier detection of minimal breast cancer (in situ and minimally invasive). Approaches and methods to conjugate different sizes and shapes of gold nanoparticles (AuNPs) with synthetic BBN analogues that maintain or enhance high breast cancer cell binding with good in vitro and in vivo stability, will be developed. The most promising targeted AuNP-BBN candidates will be evaluated in SCID mice implanted with breast tumor xenografts, to assess their ability to target breast tumors. The goal of these studies is to provide targeted AuNP-BBN analogues that could be developed, via human clinical trials, into effective molecular imaging agents for early diagnostic application in breast tumor patients. The specific objective of our application encompassing the development of new molecular imaging probes, for the early detection of breast cancer, using nanotechnology principles is directly relevant to the overall outcomes sought within the current RFA "PAR-06-475- Nanoscience and nanotechnology in Biology and Medicine (R21)". The proposed work will develop an enhancement of current Computer Tomography (CT) imaging of the breast. The research will utilize nanosized gold particles that are approximately 1000 times smaller than a human cell to generate X-ray contrast that would be detected by a CT-imaging instrument external to the body. If molecules specific to breast cancer are attached to the gold nanoparticles so that they locate in the cells of breast cancer, the contrast generated would allow the cancer to be more readily detected. This has the potential to improve the early detection and diagnosis of breast cancer.

描述（由申请人提供）：本申请描述了源自合成bombesin（BBN）类似物的新型金纳米颗粒的设计，以生产新一代的现场定向的计算机层析成像（CT）成像代理，用于特定的体内乳腺癌细胞的特异性靶向。以更特异性可视化较小的病变（以及更早的癌症检测）的总体目标，这项工作有可能提高乳腺癌的存活率。具体而言，该应用将探索靶向的金纳米颗粒是否能够产生对比度增强（增加X射线衰减），从而可以将CT用于精确，准确的功能/分子成像对乳腺癌。我们对拟议项目的具体目的是：（i）优化与肿瘤特异性肽共轭的靶向金纳米颗粒（AUNP）的合成方案； （ii）确定使用人类乳房（包括恶性病变）的拟人化幻影模型，确定CT成像中所需的金纳米颗粒的浓度； （iii）研究孟买共轭AUNP的效用，作为对植入人类乳腺癌异种移植物的SCID小鼠乳腺肿瘤的计算机断层造影（CT）成像的图像增强剂。将进行幻影研究，以评估产生足够对比度的AUNP的浓度，以有效地检测出特定设计的乳腺CT扫描仪的乳腺癌。该评估将在辐射剂量和病变的大小上进行；预计改善的对比度将导致早期发现最小的乳腺癌（原位和微创）。将开发出与合成的BBN类似物结合不同大小和形状的方法和方法，这些方法将开发出或增强高乳腺癌细胞结合具有良好体外和体内稳定性的高乳腺癌细胞。将在植入乳腺肿瘤异种移植物的SCID小鼠中评估最有希望的靶向AUNP-BBN候选物，以评估其靶向乳腺肿瘤的能力。这些研究的目的是提供有针对性的AUNP-BBN类似物，这些类似物可以通过人类临床试验发展为有效的分子成像剂，以在乳腺肿瘤患者中早期诊断应用。我们应用的具体目标包括新分子成像探针的发展，用于早期检测乳腺癌，使用纳米技术原理与当前RFA中所寻求的总体结果直接相关。拟议的工作将增强乳房当前计算机断层扫描（CT）成像。该研究将利用比人类细胞小的1000倍的纳米化金颗粒来产生X射线对比度，而X射线对比度将由人体外部的CT成像仪器检测到。如果将特定于乳腺癌的分子附着在金纳米颗粒上，以便它们位于乳腺癌细胞中，则产生的对比度将使癌症更容易被检测到。这有可能改善乳腺癌的早期检测和诊断。