Iron PARACEST MRI Contrast Agents for Monitoring Hyperthermia-based Therapy
用于监测热疗治疗的铁 PARACEST MRI 造影剂
基本信息
- 批准号:8638354
- 负责人:
- 金额:$ 9.97万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-01-01 至 2015-12-31
- 项目状态:已结题
- 来源:
- 关键词:AblationAmidesAminopyridinesChargeChemicalsChemistryColon CarcinomaComplexContrast MediaDataDependenceDepositionDevelopmentDissociationDrug AddictionDrug Delivery SystemsDrug FormulationsExtravasationFrequenciesFutureGoalsHydrocarbonsHyperthermiaImageImaging PhantomsIn VitroInduced HyperthermiaIonsIronKineticsLaboratoriesLanthanoid Series ElementsLigandsLipid BilayersLipidsLiposomal DoxorubicinLiposomesMagnetic Resonance ImagingMalignant NeoplasmsMeasurementMeasuresMetalsMethodsMonitorMusPharmaceutical PreparationsPhysiologic pulsePositioning AttributeProtonsResearchResistanceSafetyScanningSeriesSignal TransductionSystemTailTemperatureTherapeuticThermometryTimeWaterWeightalkyl groupbasechemotherapyhyperthermia treatmentimaging modalityin vivoirradiationnon-invasive imagingoxidationpublic health relevancepyridineradiofrequencytumoruptake
项目摘要
DESCRIPTION (provided by applicant): Project Summary A promising approach to target treatment resistant cancers is hyperthermia-induced release of drugs from thermally sensitive liposomes. This approach would be enabled by methods that track liposome deposition into tumor and subsequent drug release as a function of temperature. A new class of compounds containing iron (Fe(II)) coordination complexes will be developed to track liposome uptake into tumors and to monitor the liposome temperature. Our Fe(II) complexes produce contrast through chemical exchange saturation transfer (CEST) of exchangeable NH protons on amide or amino-pyridine groups that have proton resonances which are highly shifted from that of bulk water by the paramagnetic Fe(II) center (ferroCEST agents). Application of a radiofrequency pulse at the exchangeable proton resonance frequency saturates the magnetization of these protons and, through exchange, decreases the magnetization of the bulk water proton pool. Initial studies indicate that the CEST peak position of our ferroCEST agents is directly proportional to temperature over the range of 30-50 oC. This concentration independent shift leads to MRI thermometry agents that can be calibrated directly to temperature. Our specific goals are to develop Fe(II) PARACEST agents for incorporation into the lipid bilayer. These ferroCEST agents will contain long hydrocarbon tails and will be overall anionic, neutral or cationic in charge. The ferroCEST agents will be combined with commercially available lipids to form a series of liposomes, some of which are anticipated to be thermally sensitive over the desired range of 40-41 oC. The temperature dependence of the CEST peak will be determined in vitro by studies on a NMR spectrometer and in imaging phantoms on a 4.7 T MRI scanner. Initial in vivo studies of PARACEST thermometry of the Fe(II) complexes will be carried out by performing localized hyperthermia in murine colon carcinoma tumor in mice and performing CEST-imaging during treatment. Water proton frequency resonance (PFR) thermometry will be used to verify changes in tumor temperature. A long-term goal is to develop ferroCEST containing liposomes that are non-toxic, biodegradable and useful for measuring liposomal drug delivery and MR thermometry during hyperthermia or ablation therapies.
描述(由申请人提供):项目概述一种有希望的靶向治疗抗性癌症的方法是高血压诱导的药物从热敏脂质体释放。这种方法将通过跟踪脂质体沉积到肿瘤中以及随后的药物释放作为温度的函数的方法来实现。一类新的化合物含有铁(Fe(II))的配合物将被开发跟踪脂质体摄取到肿瘤和监测脂质体的温度。我们的Fe(II)配合物通过酰胺或氨基吡啶基团上的可交换NH质子的化学交换饱和转移(CEST)产生对比度,所述酰胺或氨基吡啶基团具有质子共振,所述质子共振由顺磁性Fe(II)中心(ferroCEST试剂)从本体水的质子共振高度移位。在可交换质子共振频率下施加射频脉冲使这些质子的磁化饱和,并且通过交换降低了本体水质子池的磁化。初步研究表明,我们的ferroCEST试剂的CEST峰位置在30-50 oC范围内与温度成正比。这种与浓度无关的变化导致可以直接校准到温度的MRI测温剂。我们的具体目标是开发Fe(II)PARACEST剂纳入脂质双层。这些ferroCEST试剂将含有长烃尾,并且在电荷上总体上是阴离子、中性或阳离子的。ferroCEST试剂将与市售脂质组合以形成一系列脂质体,其中一些预期在40-41 ℃的所需范围内具有热敏性。CEST峰的温度依赖性将通过在NMR光谱仪上的研究和在4.7 T MRI扫描仪上的成像体模中在体外确定。将通过在小鼠结肠癌肿瘤中进行局部热疗并在治疗期间进行CEST成像来进行Fe(II)络合物的PARACEST测温的初始体内研究。水质子频率共振(PFR)测温法将用于验证肿瘤温度的变化。长期目标是开发含有ferroCEST的脂质体,其无毒、可生物降解并且可用于在热疗或消融治疗期间测量脂质体药物递送和MR测温。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Janet Ruth Morrow其他文献
Janet Ruth Morrow的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Janet Ruth Morrow', 18)}}的其他基金
Self-assembled iron(III) hosts for MRI-guided delivery of chemotherapeutics
用于 MRI 引导化疗药物输送的自组装铁 (III) 宿主
- 批准号:
10303801 - 财政年份:2021
- 资助金额:
$ 9.97万 - 项目类别:
Self-assembled iron(III) hosts for MRI-guided delivery of chemotherapeutics
用于 MRI 引导化疗药物输送的自组装铁 (III) 宿主
- 批准号:
10405656 - 财政年份:2021
- 资助金额:
$ 9.97万 - 项目类别:
Iron paraCEST MRI Contrast Agents for Monitoring Tumor Acidosis
用于监测肿瘤酸中毒的铁 paraCEST MRI 造影剂
- 批准号:
8606835 - 财政年份:2013
- 资助金额:
$ 9.97万 - 项目类别:
Iron paraCEST MRI Contrast Agents for Monitoring Tumor Acidosis
用于监测肿瘤酸中毒的铁 paraCEST MRI 造影剂
- 批准号:
8431063 - 财政年份:2013
- 资助金额:
$ 9.97万 - 项目类别:
相似海外基金
Collaborative Research: NSF-DFG: CAS: Electrochemical Hydrogenation of Amides and Esters
合作研究:NSF-DFG:CAS:酰胺和酯的电化学氢化
- 批准号:
2140205 - 财政年份:2022
- 资助金额:
$ 9.97万 - 项目类别:
Standard Grant
Collaborative Research: NSF-DFG: CAS: Electrochemical Hydrogenation of Amides and Esters
合作研究:NSF-DFG:CAS:酰胺和酯的电化学氢化
- 批准号:
2140196 - 财政年份:2022
- 资助金额:
$ 9.97万 - 项目类别:
Standard Grant
Atroposelective Synthesis of Hindered Amides - Exploration of Synthetic Peptide Catalysts -
受阻酰胺的天体选择性合成-合成肽催化剂的探索-
- 批准号:
504378162 - 财政年份:2022
- 资助金额:
$ 9.97万 - 项目类别:
WBP Fellowship
Development of Peptide Chemical Modification Enabled by N-Halogenation of Amides
酰胺 N-卤化实现的肽化学修饰的发展
- 批准号:
22H02743 - 财政年份:2022
- 资助金额:
$ 9.97万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Modulating Signaling Endocannabinoids and Fatty Acid Amides
调节信号传导内源性大麻素和脂肪酸酰胺
- 批准号:
10532252 - 财政年份:2021
- 资助金额:
$ 9.97万 - 项目类别:
CAREER: SusChEM: Iron Catalysts for the Reduction of Amides
职业:SusChEM:用于还原酰胺的铁催化剂
- 批准号:
2146728 - 财政年份:2021
- 资助金额:
$ 9.97万 - 项目类别:
Continuing Grant
Modulating Signaling Endocannabinoids and Fatty Acid Amides
调节信号传导内源性大麻素和脂肪酸酰胺
- 批准号:
10399712 - 财政年份:2021
- 资助金额:
$ 9.97万 - 项目类别:
Function of primary fatty acid amides as lipid mediators
伯脂肪酸酰胺作为脂质介质的功能
- 批准号:
20K21285 - 财政年份:2020
- 资助金额:
$ 9.97万 - 项目类别:
Grant-in-Aid for Challenging Research (Exploratory)
Nickel-Catalyzed Alpha-Arylation of Secondary Amides
镍催化仲酰胺的α-芳基化
- 批准号:
558383-2020 - 财政年份:2020
- 资助金额:
$ 9.97万 - 项目类别:
Canadian Graduate Scholarships Foreign Study Supplements
Catalytic Synthesis of Pharmaceutical Amides in Water
水中催化合成药用酰胺
- 批准号:
EP/T01430X/1 - 财政年份:2020
- 资助金额:
$ 9.97万 - 项目类别:
Research Grant