Ultrasound Molecular Imaging to Assess Therapeutic Response

超声分子成像评估治疗反应

• 批准号: 9274263
• 负责人: Mark Andrew Borden
• 金额: $ 56.39万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-13 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9274263
• 关键词: 3-Dimensional; 3D ultrasound; Acoustics; Anatomy; Animal Model; Animals; Biological Markers; Blood Circulation; Blood Vessels; Cancer Patient; Canis familiaris; Chemistry; Client; Clinical; Clinical Trials; Complement Activation; Computers; Contrast Media; Data; Diagnosis; Disease; Dose; Early treatment; Ensure; Epitopes; Europe; Evaluation; Formulation; Goals; Gold; Human; Image; Imaging Device; Imaging technology; Immunohistochemistry; Integrin alphaVbeta3; Ionizing radiation; KDR gene; Laboratories; Ligand Binding; Ligands; Lipids; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of prostate; Measurement; Measures; Mechanics; Methods; Microbubbles; Modality; Modeling; Molecular; Molecular Target; Monitor; Morbidity - disease rate; Morphology; Motivation; Multicenter Studies; Multicenter Trials; Necrosis; Patients; Performance; Pharmacology; Physiology; Population; Price; Process; Production; Radiation; Reporting; Research; Research Personnel; Rodent; Rodent Model; Route; Safety; Scanning; Site; Soft tissue sarcoma; Specificity; Surface; System; Techniques; Technology; Testing; Therapeutic Index; Time; Tissues; Toxic effect; Traction; Translations; Treatment Efficacy; Treatment Protocols; Tumor Angiogenesis; Tumor Markers; Tumor Volume; Ultrasonography; United States; Validation; Work; X-Ray Computed Tomography; base; cancer imaging; cancer therapy; chemotherapy; clinical application; clinical diagnostics; clinical imaging; clinical translation; clinically relevant; contrast enhanced; contrast imaging; cost; disease phenotype; imaging detection; imaging modality; imaging study; imaging system; improved; laptop; molecular diagnostics; molecular imaging; new technology; novel strategies; nuclear imaging; oncology; personalized medicine; portability; preclinical study; prototype; public health relevance; response; safety study; systemic toxicity; tool; treatment response; tumor; tumor progression; working group

 DESCRIPTION (provided by applicant): Over the past decade, molecular imaging has gained traction as a powerful new imaging method to enhance the capabilities of ultrasound by providing assessment of physiology associated with disease on the cellular level. Our team has set out with the goal of developing contrast agents and ultrasound technology to substantially improve the utility of diagnostic molecular imaging for clinical translation. Thus far, our team ha achieved several highly significant advances: (1) we formulated a new type of targeted contrast agent, the buried-ligand microbubble, which is ultrasound-targeted, non-immunogenic and reduces the potential for nonspecific interactions; (2) we illustrated the utility of tailoring thesize distribution of contrast agents to improve imaging contrast; (3) we demonstrated the advantage of acoustic radiation force to enhance sensitivity in molecular imaging studies; (4) we performed acoustic radiation force-enhanced molecular imaging with an unmodified clinical ultrasound system; (5) we illustrated the need for 3-D in ultrasound molecular imaging; (6) we affirmed the utility of ultrasound molecular imaging in assessing tumor response to anti-angiogenic therapy in rodents; and (7) we demonstrated increased targeting specificity with the combination of acoustic radiation force and buried-ligand microbubbles. Several other groups working parallel to ours have corroborated our results, illustrating in rodents that ultrasound molecular imaging can provide an indication of tumor response to therapy significantly sooner than traditional methods, such as tumor size measurements. The significance of this result is that ultrasound molecular imaging can provide robust, low-cost, safe, bedside support for monitoring personalized medicine approaches in oncology. With these technological advances and promising results in rodent models, it is now time to evaluate the translatability of this technology for clinical application. To date, all reported molecular imaging studies in the US have been in small animals. In this project, we will validate the technology of ultrasound molecular imaging in a population of client-owned (pet) dogs with spontaneous soft tissue sarcomas. This large animal model is an ideal platform for validation of the clinical utility of ultrasound molecular imaging. Dogs receive similar radiation and chemotherapeutic treatments as humans, are of a size where clinical ultrasound systems can be utilized, and can be imaged with prototype molecularly targeted contrast agents without FDA and other regulatory hurdles. Thus, the goal of this project is to test the ability of ultrasound molecular imaging to detect eary response of tumors to therapy in canine patients. Patients undergoing chemotherapy will be monitored, and data will be correlated with the gold standards of DCE-CT and immunohistochemistry. This large animal, multi-center, pre-clinical study will be supported with studies to insure optimal performance of molecular imaging in the canine model, such as implementation of a 3-D interface for imaging, optimization of contrast agent and ultrasound parameters, and preliminary studies of toxicity in purpose-bred dogs. Accomplishment of our aims and validation of ultrasound molecular imaging as a treatment monitoring technique of clinical value for veterinary oncology will propel this promising technology toward human applications.

 描述（由适用提供）：在过去的十年中，分子成像作为一种强大的新成像方法获得了吸引力，以通过提供与细胞水平上与疾病相关的生理学评估来增强超声的能力。我们的团队旨在开发对比剂和超声技术，以实质上改善诊断分子成像以进行临床翻译的实用性。那远处，我们的团队达到了几个高度重大的进步：（1）我们形成了一种新型的靶向对比剂，建筑物 - 配体微气泡，它是超声靶向的，非免疫原性的，并降低了非特异性相互作用的潜力； （2）我们说明了定制对比剂的尺寸分布以改善成像对比度的实用性； （3）我们证明了声辐射力在分子成像研究中提高灵敏度的优势； （4）我们使用未修饰的临床超声系统进行了声辐射力增强的分子成像； （5）我们说明了超声分子成像中3-D的需求； （6）我们肯定了超声分子成像在评估啮齿动物中肿瘤对抗血管生成治疗的反应方面的实用性； （7）我们证明了靶向特异性与声学辐射力和建筑物 - 配体微泡的组合的提高。与我们的其他几个平行合作的组也证实了我们的结果，这在啮齿动物中说明了超声分子成像可以比传统方法（例如肿瘤大小测量）提供肿瘤对治疗的反应的指示。该结果的意义在于，超声分子成像可以为监测肿瘤学的个性化医学方法提供健壮，低成本，安全，床边的支持。随着这些技术进步和承诺在啮齿动物模型中的结果，现在是时候评估该技术在临床应用中的转换性了。迄今为止，美国所有报道的分子成像研究都在小动物中。在这个项目中，我们将验证具有赞助软组织肉瘤的客户拥有的（PET）狗的超声分子成像技术。这种大型动物模型是验证超声分子成像的临床实用性的理想平台。狗接受类似的辐射和化学治疗与人类的相似的辐射，具有可以利用临床超声系统的大小，并且可以用没有FDA和其他调节障碍的原型分子靶向对比剂进行成像。这是该项目的目的是测试超声分子成像检测犬类患者肿瘤对治疗的EARY反应的能力。接受化疗的患者将受到监测，数据将与DCE-CT和免疫组织化学的黄金标准相关。这项大型动物，多中心的临床前研究将得到研究，以确保在犬模型中确保分子成像的最佳性能，例如实施3-D界面，用于成像，优化对比剂和超声参数的优化，以及在有用的犬类中对毒性的初步研究。实现我们的目标和验证超声分子成像作为兽医肿瘤学的临床价值的治疗监测技术，将推动这项有前途的技术朝着人类的应用降低。