Exchange Transfer based Molecular MRI
基于交换转移的分子 MRI
基本信息
- 批准号:8566682
- 负责人:
- 金额:$ 30.49万
- 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:2012-08-01 至 2016-07-31
- 项目状态:已结题
- 来源:
- 关键词:2-cyclopentyl-5-(5-isoquinolylsulfonyl)-6-nitro-1H-benzo(D)imidazoleAddressAmidesBiocompatibleBiological MarkersBiopsyBlood VesselsBreastCarbohydratesCause of DeathCellsChemicalsClinicClinicalDetectionDevelopmentDiagnosisEarly DiagnosisExcisionExtracellular SpaceFourier TransformFrequenciesGlucoseGoalsHumanImageIn SituInfusion proceduresIsotopesLabelLipidsMCF7 cellMagnetic Resonance ImagingMagnetismMalignant NeoplasmsMammographyMeasuresMetabolismMethodologyMethodsMolecularMonitorMusNuclearPatientsPeptidesPerfusionPermeabilityPhysiologic pulsePilot ProjectsPositron-Emission TomographyPreventionProteinsProtocols documentationProtonsRelaxationScheduleScreening procedureSignal TransductionSliceTechnologyTechnology TransferTestingTissuesTranslatingTranslationsWaterWomanXenograft procedurebasecancer typedesignglucose metabolismimprovedin vivoin vivo Cellular and Molecular Imaging Centersmacromoleculemalignant breast neoplasmminimally invasivemortalitynovelnuclear Overhauser enhancementprogramsresearch studytheoriestumoruptakevolunteer
项目摘要
In this project, the overall goal is to design novel molecular MRI methods that are minimally invasive or
totally noninvasive and, as such, have a high potential of being translated rapidly into the clinic to be used for
tumor assessment and monitoring of treatment. Towards this goal, we exploit so-called chemical exchange
saturation transfer (CEST) contrast, which is generated through magnetic labeling of exchangeable protons
(such as NH and OH) on either exogenous or endogenous agents, followed by a physical transfer (chemical
exchange) of this label to water protons, which allows detection using MRI. To reach our ultimate goal of fast
human translation, we will focus our efforts on diamagnetic, biodegradable, non-metallic compounds.
Specifically, we will exploit the body's own building blocks, proteins and carbohydrates as CEST biomarkers
and develop MRI technology to detect these markers.
Tumors are generally characterized by an increased content of small mobile proteins and peptides,
rapid glucose metabolism, and increased permeability between blood vessels and extravascular extracellular
space. The overall goal therefore is to develop MRI pulse sequence technology and theory for detecting
mobile protein content, glucose delivery and metabolism, and tumor perfusion. Our first aim is to assess
protein content by employing nuclear interactions within these macromolecules (cross-relaxation) combined
with the exchange ofthe protein's amide protons to water protons. In the second aim, glucose metabolism
and tumor perfusion will be assessed by monitoring the uptake of non-labeled D-glucose using CEST. These
technologies are expected to be applicable for most tumor types, but to demonstrate their applicability, we
will apply them first to two human breast cancer lines: less aggressive (MCF-7) and highly aggressive and
metastatic (MDA-MB-231). This will be done both ex vivo, in perfused cells and, in vivo, on xenografts in
mice. As a third aim, we will perform pilot studies in patients to show feasibility of rapid translation.
These aims are expected to result in the availability of molecular MRI technologies in vivo that are
suitable for immediate application in humans. Once established, we expect that these methods can be used
for tumor detection, imaging tumor perfusion and metabolism, assessing tumor malignancy, and monitoring
tumor treatment. This is expected to reduce false-positive detection rates by functioning as an add-on for
current high-volume screening approaches and to improve treatment monitoring by MRI.
在这个项目中,总体目标是设计新颖的分子MRI方法,
完全非侵入性的,因此具有快速转化为临床的高潜力,
肿瘤评估和治疗监测。为了达到这个目标,我们利用所谓的化学交换
饱和转移(CEST)对比度,其通过可交换质子的磁性标记产生
(such作为NH和OH),然后进行物理转移(化学转移),
交换)到水质子,这允许使用MRI进行检测。为了达到我们的最终目标,
人类翻译,我们将集中我们的努力,抗磁性,生物降解,非金属化合物。
具体来说,我们将利用人体自身的构建模块,蛋白质和碳水化合物作为CEST生物标志物
并开发MRI技术来检测这些标记物。
肿瘤的特征通常是小的移动的蛋白质和肽的含量增加,
葡萄糖代谢迅速,血管和血管外细胞外基质之间的渗透性增加
空间因此,总体目标是发展MRI脉冲序列技术和理论,
移动的蛋白质含量、葡萄糖递送和代谢以及肿瘤灌注。我们的首要目标是评估
通过使用这些大分子内的核相互作用(交叉弛豫)组合
蛋白质的酰胺质子交换为水质子。第二个目标是葡萄糖代谢
并通过使用CEST监测未标记的D-葡萄糖的摄取来评估肿瘤灌注。这些
技术预计适用于大多数肿瘤类型,但为了证明其适用性,我们
将首先将它们应用于两种人类乳腺癌细胞系:低侵袭性(MCF-7)和高侵袭性,
转移性(MDA-MB-231)。这将在离体灌注细胞和体内异种移植物上进行。
小鼠作为第三个目标,我们将在患者中进行试点研究,以显示快速翻译的可行性。
这些目标预计将导致分子MRI技术在体内的可用性,
适合于立即应用于人体。一旦建立,我们预计这些方法可以用于
用于肿瘤检测、肿瘤灌注和代谢成像、评估肿瘤恶性程度和监测
肿瘤治疗预计这将减少假阳性检测率,
目前的高容量筛查方法,并通过MRI改善治疗监测。
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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Peter CM Van Zijl其他文献
Peter CM Van Zijl的其他文献
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{{ truncateString('Peter CM Van Zijl', 18)}}的其他基金
TRD 3: MRI parameters reflecting tissue composition and microstructure
TRD 3:反映组织成分和微观结构的 MRI 参数
- 批准号:
10270100 - 财政年份:2021
- 资助金额:
$ 30.49万 - 项目类别:
TRD 3: MRI parameters reflecting tissue composition and microstructure
TRD 3:反映组织成分和微观结构的 MRI 参数
- 批准号:
10439905 - 财政年份:2021
- 资助金额:
$ 30.49万 - 项目类别:
TRD 3: MRI parameters reflecting tissue composition and microstructure
TRD 3:反映组织成分和微观结构的 MRI 参数
- 批准号:
10614612 - 财政年份:2021
- 资助金额:
$ 30.49万 - 项目类别:
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