Detection of in vivo enzyme activities with CEST MRI
使用 CEST MRI 检测体内酶活性
基本信息
- 批准号:8495297
- 负责人:
- 金额:$ 49.87万
- 依托单位:
- 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:2012-07-01 至 2017-05-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAntigensBiological MarkersBreastCadaverineChelating AgentsChemical AgentsChemicalsChemotherapy-Oncologic ProcedureClinicClinicalClinical assessmentsContrast MediaDU145DetectionDevelopmentEngineeringEnzyme Inhibitor DrugsEnzyme InhibitorsEnzymesEvaluationGlutamate Carboxypeptidase IIGoalsImageIn VitroIndividualInjection of therapeutic agentLigandsLinkLocationMagnetic Resonance ImagingMalignant NeoplasmsMalignant neoplasm of pancreasMalignant neoplasm of prostateMeasurementMeasuresMedicineMethodologyMethodsModelingMonitorMusPancreasPatientsPerformancePhysiologic pulseProstateProteinsProtocols documentationResearchRoleSignal TransductionStagingTestingTherapeutic EffectTissuesTransglutaminasesTranslationsTreatment ProtocolsTumor TissueUrokinaseVCaPValidationcancer diagnosiscancer typechemotherapydesignenzyme activityextracellularfluorescence imagingfluorophorehuman cancer mouse modelimprovedin vivoinhibitor/antagonistinnovationmalignant breast neoplasmmeetingsmouse modelpinacolyl methylphosphonic acidpre-clinicalpreclinical studyprotein expressionresponsesuccesstumortumor growthtumor microenvironment
项目摘要
ABSTRACT
Enzyme activities are important biomarkers for cancer diagnoses and assessing chemotherapies. We have
developed MRI contrast agents that are detected via Chemical Exchange Saturation Transfer (CEST) and that
are responsive to enzyme activity. We have also developed CEST MRI methods that can detect these agents
within in vivo tumor tissues in mouse models of human cancers. Importantly, we can selectively detect an
enzyme-responsive agent and an unresponsive "control" agent during the same study in the same tissue
location, which improves our evaluation of enzyme activity within the mouse model. Just as multiple
fluorophores have revolutionized the evaluation of enzyme activities during in vitro and ex vivo studies, CEST
agents and CEST MRI has potential to revolutionize the evaluation of enzyme activities in vivo.
We propose to build on our recent research successes by linking enzyme-responsive and control agents to
create a dimeric agent, by comparing paramagnetic and diamagnetic CEST agents, and by optimizing the
saturation period of the CEST MRI acquisition protocol in order to improve the detection sensitivity of CEST
MRI. We also propose to develop enzyme-responsive CEST agents that semi-quantitatively detect the
activities of urokinase Plasminogen Activator (uPA) in mouse models of pancreatic cancer, Prostate Specific
Membrane Antigen (PSMA) in mouse models of prostate cancer, and transglutaminase (TG2) in mouse
models of breast cancer. We propose to use these CEST agents and our in vivo CEST MRI methodology to
investigate three biomedical aims: A) to predict the effect of chemotherapies before they are administered to
mouse models; B) to evaluate early response to chemotherapies; C) to investigate our hypothesis that enzyme
activity is a more accurate biomarker than enzyme expression for predicting and evaluating therapeutic effects.
Together, these studies address our overarching goal of eventually using CEST agents and CEST MRI to tailor
the choice of chemotherapy and treatment regimen for each individual patient, in order to support the paradigm
of personalized medicine.
摘要
酶活性是癌症诊断和评估化疗的重要生物标志物。我们有
开发了通过化学交换饱和转移(CEST)检测的MRI造影剂,
对酶的活性有反应。我们还开发了CEST MRI方法,可以检测这些代理人
在人类癌症小鼠模型的体内肿瘤组织中。重要的是,我们可以选择性地检测
在相同组织中的相同研究期间,酶反应剂和无反应“对照”剂
位置,这改善了我们对小鼠模型内酶活性的评估。同样多的
荧光团在体外和离体研究中彻底改变了酶活性的评价,
试剂和CEST MRI具有彻底改变体内酶活性评价的潜力。
我们建议在我们最近的研究成功的基础上,将酶反应剂和控制剂联系起来,
通过比较顺磁性和反磁性CEST试剂,并通过优化
CEST MRI采集协议的饱和期,以提高CEST的检测灵敏度
核磁共振我们还建议开发酶反应CEST试剂,半定量检测
尿激酶纤溶酶原激活物(uPA)在胰腺癌小鼠模型中的活性,前列腺特异性
前列腺癌小鼠模型中的膜抗原(PSMA)和小鼠中的转氨酶(TG 2)
乳腺癌的模型我们建议使用这些CEST试剂和我们的体内CEST MRI方法,
研究三个生物医学目的:A)在化疗之前预测化疗的效果,
小鼠模型; B)评估对化疗的早期反应; C)研究我们的假设,
活性是比酶表达更准确的生物标志物,用于预测和评估治疗效果。
总之,这些研究解决了我们的总体目标,即最终使用CEST试剂和CEST MRI来定制
为每个患者选择化疗和治疗方案,以支持范例
个性化医疗。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Mark David Pagel其他文献
Mark David Pagel的其他文献
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{{ truncateString('Mark David Pagel', 18)}}的其他基金
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- 批准号:
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- 资助金额:
$ 49.87万 - 项目类别:
Exploiting Melanin Synthesis to Improve Tumor Detection with Multispectral Optoacoustic Tomography and Optical Guided Surgery
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Measuring extracellular pH in pre-clinical tumor models with CEST MRI
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Detection of in vivo enzyme activities with CEST MRI
使用 CEST MRI 检测体内酶活性
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Measuring extracellular pH in pre-clinical tumor models with CEST MRI
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Detection of in vivo enzyme activities with CEST MRI
使用 CEST MRI 检测体内酶活性
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