Cerenkov-emission based nanosensors to detect biologic activities in vivo

基于切伦科夫发射的纳米传感器检测体内生物活性

基本信息

批准号：
8788930
负责人：
Jan Grimm
金额：
$ 40.33万
依托单位：
SLOAN-KETTERING INST CAN RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-04-01 至 2017-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8788930
关键词：
Animals Biocompatible Coated Materials Biological Cadmium Cathepsins B Cell physiology Cells Charge Clinical Contrast Media Copper Data Dextrans Disease Early Diagnosis Electrons Enzymes Event Fluorescein Fluorochrome Funding Gelatinase A Generations Goals Gold Heavy Metals Histology Image Inflammation Knowledge Life Light Lipids Magnetic Resonance Magnetic Resonance Imaging Malignant Neoplasms Measures Medicine Methodology Methods Modality Molecular Molecular Target Monitor Normal Cell Nuclear Optics Outcome Study Particulate Peptide Hydrolases Peptides Physical activity Positron Positron-Emission Tomography Process Proteins Quantum Dots Radioactive Radioactivity Radioisotopes Reading Refractive Indices Relative (related person)Research Signal Transduction Silicon Dioxide Site System Technology Testing Time Tissues Toxic effect Travel United States National Institutes of Health Urokinase Water Work Zirconium attenuation base clinical application design imaging agent improved in vivo in vivo imaging inhibitor/antagonist innovation intraoperative imaging iron oxide lightspeed luminescence molecular imaging nanoparticle nanosensors optical imaging particle pre-clinical radiotracer response tool tumor uptake zirconium oxide

项目摘要

DESCRIPTION (provided by applicant): Activatable optical and magnetic resonance contrast agents have been devised to sense and visualize molecular activity in vivo. However, though highly sensitive, nuclear imaging has been limited considerably in sensing biological activities by the physical inability to switch radioactivity "on" or "off". To fill this gap, we hypothesize that Cerenkov luminescence imaging in conjunction with nanoparticles can be utilized to create activatable nanosensors based on radioactive decay. Blue Cerenkov light is generated by the passage of particulate radioactive emissions (such as positrons or electrons) through tissues. Cerenkov light allows for optical imaging of radiotracers with highly sensitive cameras. Based on the results of our previously demonstrated in vivo Cerenkov luminescence imaging from radiotracers, the overall objective of this application is to sense enzymatic activities associated with cancer in vivo using radiometals and modified nanoparticles In this new R01 application, cancer-related endoproteases modulate the physical interaction between different nanoparticles and a radiometals as Cerenkov emitters. Our hypothesis will be tested in three specific aims on the basis of strong preliminary data from our lab: in Specific Aim (1), we will explore different design principles of the nanoparticles in evaluating the efect of diferent coatings and radiometals onto the Cerenkov emission; in Specific Aim (2), we will sense the enzymatic activity of specific endoproteases (matrix metalloproteinase-2, cathepsin B and urokinase-type plasminogen activator) in vivo using Cerenkov imaging; in Specific Aim (3), the objective is to implement a process to quantify the nanosensor's activation and thus the enzymatic activity. This is based on a combination of Cerenkov imaging with positron emission tomography (PET) imaging. PET imaging allows for an independent quantification of the nanosensors in the tumor (using the Specific Uptake Value (SUV)) irrespective of their current activation state. We propose an inherent method to correct for the tissue attenuation and to perform a relative quantification of the signal and thus enzymatic activity. We believe that the proposed research constitutes an innovative direction and a paradigm shift in molecular imaging as it allows for sensing of enzymatic activity with radiotracers with an optical read-out, combining the unique sensitivity of PET and optical imaging together. The contribution of the proposed research is significant as it expands the potential application for nuclear imaging. It provides an entire new path for radiotracers to detect relevant biological signals. These nanosensors could ultimately find their way into the clinical realm, for example in intraoperative imaging.

描述（由申请人提供）：已设计出可激活的光学和磁共振对比剂来感知和可视化体内分子活性。然而，尽管高度敏感，但核成像在传感生物学活动中的限制很大物理无法切换放射性“ ON”或“ OFF”。为了填补这一空白，我们假设 Cerenkov发光成像与纳米颗粒结合使用，可以利用基于放射性衰减创建可激活的纳米传感器。蓝色的Cerenkov光是通过组织通过颗粒放射性排放（例如正电子或电子）通过组织而产生的。 Cerenkov Light允许具有高敏感相机的放射性示例的光学成像。基于我们先前证明的放射性示例中的体内Cerenkov发光成像的结果，该应用的总体目的是感知相关的酶促活动在这种新的R01应用中，使用辐射量和改性纳米颗粒的体内癌症，与癌症相关的内螺旋蛋白酶调节了不同纳米颗粒和辐射仪之间的物理相互作用，作为Cerenkov发射器。我们的假设将根据我们实验室的强烈初步数据进行三个特定目的检验：在特定目的（1）中，我们将探索纳米颗粒的不同设计原理，以评估差异涂层和放射线的影响cerenkov发射；在特定的目标（2）中，我们将使用Cerenkov成像在体内感觉到特定内螺旋蛋白酶（基质金属蛋白酶2，组织蛋白酶-2和尿激酶型纤溶酶原激活剂）的酶活性；在特定目的（3）中，目标是实施一个量化纳米传感器激活的过程，从而量化了酶促活性。这是基于Cerenkov成像与正电子发射断层扫描（PET）成像的组合。 PET成像允许对肿瘤中的纳米传感器进行独立的定量（使用特定摄取值（SUV）），无论其当前激活状态如何。我们提出了一种固有的方法，以校正组织衰减并进行信号的相对定量，从而进行酶促活性。我们认为，所提出的研究构成了创新的方向和分子成像的范式转移，因为它可以通过光学读出的放射性读数来传感酶活性，并将PET和光学成像的独特灵敏度结合在一起。拟议的研究的贡献很重要，因为它扩大了潜在的核成像应用。它为放射性示踪剂检测相关的生物学信号提供了一条全新的途径。这些纳米传感器最终可以进入临床领域，例如术中成像。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Cerenkov imaging.

DOI：
10.1016/b978-0-12-411638-2.00006-9
发表时间：
2014
期刊：
ADVANCES IN CANCER RESEARCH
影响因子：
0
作者：
Das, Sudeep;Grimm, Jan;Thorek, Daniel L. J.
通讯作者：
Thorek, Daniel L. J.

Near-Infrared Intraoperative Chemiluminescence Imaging.

DOI：
10.1002/cmdc.201600301
发表时间：
2016-09-20
期刊：
CHEMMEDCHEM
影响因子：
3.4
作者：
Buechel, Gabriel E.;Carney, Brandon;Shaffer, Travis M.;Tang, Jun;Austin, Christine;Arora, Manish;Zeglis, Brian M.;Grimm, Jan;Eppinger, Jorg;Reiner, Thomas
通讯作者：
Reiner, Thomas

Optical Imaging of Ionizing Radiation from Clinical Sources.

DOI：
10.2967/jnumed.116.178624
发表时间：
2016-11
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
0
作者：
Shaffer TM;Drain CM;Grimm J
通讯作者：
Grimm J

Utilizing the power of Cerenkov light with nanotechnology.

利用切伦科夫光的力量和纳米技术。