Molecular Photoacoustic Imaging for Diagnostics and Therapy Monitoring

用于诊断和治疗监测的分子光声成像

基本信息

批准号：
10631940
负责人：
Richard R Bouchard
金额：
$ 60.33万
依托单位：
UNIVERSITY OF TX MD ANDERSON CAN CTR
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10631940
关键词：
3-Dimensional Acceleration Address Algorithms Anatomy Animal Disease Models Animal Model Animals Antibodies Binding Biochemical Biodistribution Blood Cancer Center Cell Culture Techniques Cholesterol Clinical Commercial grade Communities Complement Contrast Media Coupled Data Detection Development Diagnostic Imaging Disease Doctor of Medicine Drug Delivery Systems Drug Kinetics Drug Targeting Dyes Encapsulated Epidermal Growth Factor Receptor Evaluation Foundations Functional Imaging Future Generations Goals Hemoglobin Image Imaging Device Imaging Techniques Imaging technology Indocyanine Green Label Letters Lighting Liposomes Malignant neoplasm of ovary Mediating Medical Medical Research Modeling Molecular Molecular Target Monitor Morphology Neoplasms Optics Outcome Oxygen Pathologic Processes Pathology Penetration Phospholipids Physiologic pulse Physiological Positioning Attribute Process Production Property Protocols documentation Quality Control Reproducibility Research Personnel Research Proposals Resolution Safety Sensitivity and Specificity Signal Transduction Silicon Dioxide Specificity System Technology Therapeutic Tissues Toxic effect Translational Research Translations Validation Visualization absorption bioluminescence imaging biomarker evaluation cancer therapy cellular imaging clinical translation contrast imaging detection limit drug discovery fundamental research image processing imaging approach imaging capabilities imaging modality imaging platform imaging system improved in vivo industry partner interest large scale production millimeter molecular imaging molecular marker monomer mouse model nanoGold nanorod neoplastic cell novel optical imaging personalized medicine pharmacologic photoacoustic imaging pre-clinical research preclinical imaging preclinical study prevent quantitative imaging scale up tomography tool treatment response

项目摘要

PROJECT SUMMARY Small-animal models are powerful discovery tools in medical research, but sacrificing prevents long-term, in vivo observation of natural or pathological processes. As such, there is a need for a morphologic, functional, cellular/molecular, and quantitative imaging technique capable of longitudinal visualization of biochemical and pharmacological processes in small-animal disease models. Unfortunately, current molecular optical imaging approaches tend to present an undesirable trade-off between imaging depth and resolution. Non-invasive photoacoustic imaging (PAI), which is capable of simultaneous anatomical, functional, and molecular visualization of pathology with high contrast/resolution at depth, has thus generated significant excitement among preclinical imaging researchers. However, these end-users currently lack a reliable, reproducible, and validated molecular PAI platform to complement their translational research. To address this need, we propose enabling the molecular sensitivity of PAI through the development and validation of targeted contrast agents and signal/image processing algorithms to allow simultaneous, reproducible, quantitative, longitudinal, and tomographic imaging of molecular and physiological signatures of disease and therapy response in preclinical studies. Many available molecular contrast agents lack adequate PAI contrast for deep imaging and/or overlap with spectral features of hemoglobin absorption, making it difficult to differentiate a targeted probe from surrounding blood. To address these limitations, we seek to continue development of a unique contrast agent based on antibody-targeted liposomes loaded with J-aggregates of indocyanine green (ICG) dye. Encapsulation of ICG J-aggregates in a liposomal compartment results in a stable contrast agent (Lipo-JICG), which provides highly advantageous properties for in vivo PAI: (i) a strong, narrow absorbance at ~890 nm, where it can be readily unmixed from hemoglobin spectra; (ii) enhancement of PAI signal due to dye-aggregation-mediated increases in thermal gradients and absorbance; (iii) the ability to implement robust, semi-quantitative PAI analysis that does not interfere with imaging of important physiological parameters such as blood oxygen saturation. Our compelling preliminary data show that targeted Lipo-JICG provides impressive stability, linearity, PAI-signal intensity and molecular specificity. During this research proposal, we will validate the molecular- imaging capabilities of this promising technology in tissue-mimicking phantoms, well-characterized cell cultures, and orthotopic models of ovarian cancer. At the conclusion of these studies, we will be in position to start mass- production and end-user dissemination of Lipo-JICG and image processing algorithms as a fully validated, molecularly specific PAI platform for reliable, reproducible, and affordable preclinical imaging. Although not the principle objective of this proposal, these studies also provide a foundation for clinical translation of our agent as the liposomes, ICG, and humanized-targeted antibodies of which it is composed have all been FDA cleared for i.v. use, therefore reducing safety concerns and improving the chances for future clinical utilization.

项目概要小动物模型是医学研究中强大的发现工具，但牺牲会阻碍长期的体内研究观察自然或病理过程。因此，需要一种形态学、功能性、细胞/分子和定量成像技术，能够纵向可视化生化和小动物疾病模型中的药理过程。不幸的是，当前的分子光学成像方法往往会在成像深度和分辨率之间出现不希望的权衡。非侵入性光声成像（PAI），能够同时进行解剖、功能和分子成像病理可视化在深度上具有高对比度/分辨率，因此引起了极大的兴奋临床前成像研究人员中。然而，这些最终用户目前缺乏可靠的、可重复的、经过验证的分子 PAI 平台来补充他们的转化研究。为了满足这一需求，我们建议通过开发和验证靶向造影剂来实现 PAI 的分子敏感性信号/图像处理算法允许同时、可重复、定量、纵向和临床前疾病和治疗反应的分子和生理特征的断层扫描成像研究。许多可用的分子造影剂缺乏足够的 PAI 对比度来进行深度成像和/或重叠具有血红蛋白吸收的光谱特征，使得很难将目标探针与周围的血液。为了解决这些限制，我们寻求继续开发独特的造影剂基于负载有吲哚菁绿 (ICG) 染料 J 聚集体的抗体靶向脂质体。封装脂质体隔室中的 ICG J-聚集体产生稳定的造影剂 (Lipo-JICG)，它提供体内 PAI 的非常有利的特性：(i) 在 ~890 nm 处具有强而窄的吸光度，在该处可以很容易从血红蛋白光谱中分离出来； (ii) 染料聚集介导的 PAI 信号增强热梯度和吸光度增加； (iii) 实施稳健、半定量 PAI 的能力不干扰血氧等重要生理参数成像的分析饱和。我们令人信服的初步数据表明，靶向 Lipo-JICG 提供了令人印象深刻的稳定性、线性度、 PAI-信号强度和分子特异性。在这项研究计划中，我们将验证分子- 这种有前途的技术在模拟组织模型、充分表征的细胞培养物中的成像能力，和卵巢癌的原位模型。在这些研究结束时，我们将能够开始大规模- Lipo-JICG 的生产和最终用户传播以及图像处理算法作为经过充分验证的、分子特异性 PAI 平台，可实现可靠、可重复且经济实惠的临床前成像。虽然不是该提案的主要目标，这些研究也为我们的药物的临床转化提供了基础其组成的脂质体、ICG 和人源化靶向抗体均已获得 FDA 批准静脉注射使用，从而减少安全问题并提高未来临床使用的机会。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Antibody-Conjugated Polymersomes with Encapsulated Indocyanine Green J-Aggregates and High Near-Infrared Absorption for Molecular Photoacoustic Cancer Imaging.

具有封装的吲哚菁绿 J 聚集体和高近红外吸收的抗体缀合聚合物体，用于分子光声癌症成像。

DOI：
10.1021/acsami.3c16584
发表时间：
2024-01-25
期刊：
ACS applied materials & interfaces
影响因子：
9.5
作者：
Mohammed R Kawelah;Sangheon Han;Ceren Atila Dincer;Jongyeong Jeon;Joel Brisola;Aasim F Hussain;A. Jeevarathinam;Richard R Bouchard;A. Marras;Thomas M. Truskett;Konstantin V Sokolov;Keith P Johnston
通讯作者：
Keith P Johnston