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Optical Imaging of Targeted Anti-Cancer Drug Delivery Kinetics

靶向抗癌药物输送动力学的光学成像

基本信息

批准号：
8996138
负责人：
Kevin J Webb
金额：
$ 16.75万
依托单位：
PURDUE UNIVERSITY
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：
2015-01-16 至 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8996138
关键词：
Adverse effects Affect Antineoplastic Agents Bayesian Modeling Cardiovascular Diseases Cessation of life Chemicals Chemistry Cleaved cell Clinic Colon Carcinoma Contrast Media Diffusion Disease Drug Delivery Systems Drug Design Drug Kinetics Drug Targeting Fluorescence Fluorescence Resonance Energy Transfer Folic Acid Future Geometry Goals Health Heart Diseases Human Image Inflammation Kinetics Knowledge Lasers Length Lung Malignant Neoplasms Malignant neoplasm of brain Maps Measures Medical Research Methods Microscopy Modeling Molecular Mus North America Optics Ovarian Performance Pharmaceutical Preparations Positioning Attribute Process Renal carcinoma Research Scanning Spectrum Analysis Surface Techniques Time Tissues Toxic effect Tumor Tissue Universities Work cancer cell cancer therapy chemical kinetics chemotherapy design disulfide bond reduction drug development fluorophore folate-binding protein imaging modality improved in vivo interest light scattering macrophage malignant breast neoplasm molecular imaging mouse model nanometer nervous system disorder optical imaging response stem targeted imaging targeted treatment tomography tool tumor two-photon uptake

项目摘要

DESCRIPTION (provided by applicant): Optical Imaging of Targeted Anti-Cancer Drug Delivery Kinetics: Project Summary Kevin Webb and Philip Low, Purdue University We propose to determine anti-cancer drug delivery kinetics in vivo using an optical molecular imaging method with nanometer length scale sensitivity. This imaging method will extract fluorescence resonance energy transfer (FRET) parameter images from heavily scattered light through optical diffusion tomography (ODT). Our goal is to establish efficacy in determining targeted anti-cancer drug delivery kinetics. To improve image quality and reduce the computational burden, the subject geometry will be determined using a laser line scan, and an unstructured mesh diffusion model will describe the optical transport. With a folate-targeted FRET indicator, mouse tumors will be imaged in vivo and results compared with those from the euthanized, dissected mice. Once a folate-FRET chemical is internalized into a cancer cell, a disulfide bond reduction causes the acceptor that acted as a quencher to be cleaved from the donor. This cleavage results in increased donor emission and reduced acceptor emission associated with the increase in distance between the donor and acceptor fluorophores. These FRET parameters imaged over time will provide the necessary information to develop spatial maps of the release kinetics. Prior studies have shown that conjugation of either the FRET chemical or the anti-cancer drug to folate does not affect the folate uptake into cancer cells, meaning that the folate-FRET parameters will offer accurate information about folate-drug kinetics. The proposed work will result in quantitative in vivo spatial maps of the number of released acceptor fluorophores as a function of time. Although anti-cancer drugs will not be used in this research, inference for their performance follows because of the identical release process, upon which the drug is activated. Once established, this optical imaging approach will become a tool in the design of new anti-cancer drugs.

描述（由申请人提供）：靶向抗癌药物递送动力学的光学成像：项目总结Kevin Webb和Philip Low，普渡大学我们建议使用具有纳米长度尺度灵敏度的光学分子成像方法来确定抗癌药物在体内的传递动力学。这种成像方法将通过光学扩散断层扫描（ODT）从严重散射的光中提取荧光共振能量转移（FRET）参数图像。我们的目标是建立确定靶向抗癌药物递送动力学的功效。为了提高图像质量并减少计算负担，将使用激光线扫描确定受试者的几何形状，并且非结构化网格扩散模型将描述光学传输。使用叶酸靶向FRET指示剂，将对小鼠肿瘤进行体内成像，并将结果与来自安乐死的解剖小鼠的结果进行比较。一旦叶酸-FRET化学物质被内化到癌细胞中，二硫键还原导致作为猝灭剂的受体从供体中裂解。这种切割导致与供体和受体荧光团之间的距离增加相关的供体发射增加和受体发射减少。这些FRET参数随时间成像将提供必要的信息，开发释放动力学的空间图。先前的研究已经表明，FRET化学品或抗癌药物与叶酸的缀合不影响癌细胞对叶酸的摄取，这意味着叶酸-FRET参数将提供有关叶酸-药物动力学的准确信息。拟议的工作将导致在体内释放受体荧光团的数量作为时间的函数的定量空间图。虽然抗癌药物将不用于本研究，但由于药物被激活的相同释放过程，因此可以推断其性能。一旦建立，这种光学成像方法将成为设计新抗癌药物的工具。