Ultrasound Molecular Imaging to Assess Therapeutic Response

超声分子成像评估治疗反应

基本信息

批准号：
9440982
负责人：
Mark Andrew Borden
金额：
$ 57.23万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-13 至 2021-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9440982
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 Prediction of Response to Therapy 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 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

项目摘要

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（由申请人提供）：在过去的十年中，分子成像作为一种强大的新成像方法受到关注，通过在细胞水平上提供与疾病相关的生理学评估来增强超声的能力，我们的团队已经设定了目标。开发造影剂和超声技术以大幅提高诊断分子成像在临床转化中的实用性到目前为止，我们的团队取得了几项非常重要的进展：（1）我们配制了一种新型靶向造影剂，即埋藏配体微泡。，即（2）我们展示了调整造影剂的尺寸分布以提高成像对比度的效用；（3）我们展示了声辐射力在分子成像研究中增强超声灵敏度的优势；（4）我们进行了声辐射力增强。使用未经修改的临床超声系统进行分子成像；（5）我们说明了超声分子成像中 3D 的必要性；（6）我们肯定了超声分子成像在评估肿瘤反应中的实用性。啮齿类动物的抗血管生成治疗；（7）我们证明了声辐射力和埋藏配体微泡的结合可以提高靶向特异性，与我们并行工作的其他几个小组也证实了我们的结果，说明超声分子成像可以在啮齿类动物中提供。肿瘤对治疗的反应明显比传统方法（例如肿瘤大小测量）更快，这一结果的意义在于，超声分子成像可以为监测肿瘤学中的个性化医疗方法提供强大、低成本、安全的床边支持。这些技术进步和在啮齿动物模型中取得的有希望的结果，现在是时候评估该技术在临床应用中的可转化性了。迄今为止，美国所有报道的分子成像研究都在小动物中进行。该大型动物模型是验证超声分子成像临床效用的理想平台，狗接受与人类类似的放射和化疗治疗。，其尺寸为临床可以使用超声系统，并且可以使用原型分子靶向造影剂进行成像，而无需 FDA 和其他监管障碍。因此，该项目的目标是测试超声分子成像检测犬患者肿瘤对治疗的早期反应的能力。将监测接受化疗的患者，并将数据与 DCE-CT 和免疫组织化学的金标准相关联。这项大型动物、多中心、临床前研究将得到研究的支持，以确保犬类分子成像的最佳性能。模型，例如用于成像的 3D 界面的实现、造影剂和超声参数的优化以及对专门饲养的狗的毒性的初步研究以及超声分子成像作为临床价值的治疗监测技术的验证。兽医肿瘤学将推动这项有前途的技术走向人类应用。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Photoacoustic technique to measure temperature effects on microbubble viscoelastic properties.

光声技术测量温度对微泡粘弹性特性的影响。

DOI：
10.1063/1.5005548
发表时间：
2018-03-14
期刊：
Applied physics letters
影响因子：
4
作者：
J. Lum;D. Stobbe;M. Borden;T. Murray
通讯作者：
T. Murray

The effect of size range on ultrasound-induced translations in microbubble populations.

尺寸范围对微泡群体中超声诱导翻译的影响。

DOI：
发表时间：
2020
期刊：
影响因子：
0
作者：
Supponen, Outi;Upadhyay, Awaneesh;Lum, Jordan;Guidi, Francesco;Murray, Todd;Vos, Hendrik J;Tortoli, Piero;Borden, Mark
通讯作者：
Borden, Mark

Click Conjugation of Cloaked Peptide Ligands to Microbubbles.

单击隐藏肽配体与微泡的缀合。