Molecular Photoacoustic Imaging using Multitargeted Contrast Agents

使用多靶点造影剂的分子光声成像

• 批准号: 8203467
• 负责人: Carolyn Louise Bayer
• 金额: $ 5.11万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8203467
• 关键词: Anatomy; Animal Model; Biocompatible Materials; Biological; Biopsy; Cancer Biology; Cancerous; Cell model; Cell physiology; Cells; Characteristics; Collaborations; Communication; Complex; Contrast Media; Correlation Studies; Development; Diagnostic Imaging; Disease; Disease Progression; Early Diagnosis; Endocytosis; Enrollment; Epidermal Growth Factor Receptor; Ethics; Fellowship; Gel; Generations; Goals; Gold; Human; Image; Imaging Techniques; In Vitro; Injection of therapeutic agent; Integrins; Knowledge; Lasers; Longitudinal Studies; Malignant Neoplasms; Mammary Neoplasms; Measures; Medical Imaging; Mentors; Mentorship; Methods; Modeling; Molecular; Monitor; Mus; Optics; Patients; Pharmaceutical Preparations; Physiology; Property; Regulation; Research; Research Personnel; Resolution; Signal Transduction; Staging; System; Technical Expertise; Therapeutic Effect; Tissues; Training; Tyrosine Kinase Inhibitor; Ultrasonography; Variant; Water; absorption; angiogenesis; animal tissue; cellular targeting; chromophore; computerized data processing; design; imaging modality; improved; in vivo; lapatinib; malignant breast neoplasm; molecular imaging; molecular scale; molecular/cellular imaging; nanoparticle; nanorod; neoplastic cell; optical imaging; plasmonics; receptor; receptor expression; response; skills; small molecule; treatment planning; tumor; tumor growth; tumor xenograft; uptake

DESCRIPTION (provided by applicant): The proposed research seeks to use integrated photoacoustic imaging and ultrasound, combined with molecularly targeted contrast agents, to acquire non-invasive in vivo molecular images of tumor cell receptor expression. While methods of molecular imaging have been developed, challenges with spatial resolution, depth of field, temporal resolution and sensitivity remain. Multimodal photoacoustic and ultrasound imaging combines advantageous features of optical and ultrasound imaging, enabling optical probing of contrast at a high resolution at a depth of several centimeters in vivo. The proposed research seeks to demonstrate photoacoustic molecular imaging of tumor receptor expression. The hypothesis is that photoacoustic imaging with multiplex targeted contrast agents, combined with high resolution ultrasound imaging, will provide the necessary sensitivity and resolution to detect and distinguish between regions of in vivo tumors which are expressing different receptors. The first aim of the project is to demonstrate in vitro photoacoustic imaging of multiplex targeted contrast agents which have been endocytosed in cells expressing the relevant receptor. Inclusions containing targeted cells will then be injected in ex vivo animal tissue and imaged using multispectral photoacoustics in order to develop statistical correlations to distinguish between contrast agents with varying optical properties, and native tissue chromophores. The second aim will demonstrate in vivo photoacoustic and ultrasound imaging of complex tumor receptor expression within cancer tumor xenografts in murine animal models using injections of the multiplex targeted contrast agents. The third aim will perform longitudinal studies on tumor growth and response to drug treatment within the murine model, using the combined photoacoustic and ultrasound imaging techniques to image targeted contrast agents uptaken within the tumor. The training plan proposed to accomplish these goals has been designed to establish trainee mentors with specific technical expertise. The selected mentors are experts in ultrasound and photoacoustic imaging; the synthesis and applications of plasmonic nanoparticles for biomedical applications; and the cell expression and regulation of cancer; respectively. The PI will enroll in formal training in the ethical conduct of research and in training specific to her research field, to prepare her for independent research. PUBLIC HEALTH RELEVANCE: The development of non-invasive molecular imaging methods capable of providing detailed information on diseased tissues would enable the earlier diagnosis of disease, the development of tailored treatment plans, and improved monitoring of disease progression. To achieve this goal, this research proposes the use of a combination of photoacoustic and ultrasound imaging using cellularly-targeted gold nanorods as uniquely distinguishable imaging contrast agents.

描述（由申请人提供）：拟进行的研究旨在利用光声成像和超声结合分子靶向造影剂，获得肿瘤细胞受体表达的非侵入性体内分子图像。虽然分子成像方法已经发展起来，但在空间分辨率、景深、时间分辨率和灵敏度方面仍然存在挑战。多模态光声和超声成像结合了光学和超声成像的优点，使光学探测在体内几厘米深度的高分辨率对比度。提出的研究旨在证明肿瘤受体表达的光声分子成像。我们的假设是，光声成像与多重靶向造影剂相结合，结合高分辨率超声成像，将提供必要的灵敏度和分辨率来检测和区分体内肿瘤表达不同受体的区域。该项目的第一个目的是证明在体外光声成像的多重靶向造影剂已经内吞在细胞表达相关受体。然后将含有目标细胞的内含物注射到离体动物组织中，并使用多光谱光声学成像，以建立统计相关性，以区分具有不同光学特性的造影剂和天然组织发色团。第二个目标是通过注射多重靶向造影剂，在小鼠动物模型中展示肿瘤异种移植物中复杂肿瘤受体表达的体内光声和超声成像。第三个目标将在小鼠模型中对肿瘤生长和对药物治疗的反应进行纵向研究，使用联合光声和超声成像技术对肿瘤内吸收的靶向造影剂进行成像。为实现这些目标而提出的培训计划旨在建立具有具体技术专门知识的培训导师。入选导师为超声、光声成像方面的专家；生物医学用等离子体纳米粒子的合成与应用以及肿瘤细胞的表达和调控；分别。PI将参加研究伦理行为方面的正式培训，并接受针对其研究领域的培训，为独立研究做好准备。