HYPOXIA / PERFUSION IMAGING - USING MICROPET WITH (62)CU-PTSM/(62)CU-ATSM
缺氧/灌注成像 - 使用带有 (62)CU-PTSM/(62)CU-ATSM 的微型PET
基本信息
- 批准号:7601212
- 负责人:
- 金额:$ 1万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-07-01 至 2008-06-30
- 项目状态:已结题
- 来源:
- 关键词:AnimalsAutoradiographyComputer Retrieval of Information on Scientific Projects DatabaseContrast MediaCountEF5FundingGliomaGrantHalf-LifeHypoxiaImageImmunohistochemistryIndividualInstitutionLifeMeasurementMeasuresMethodsModalityPerfusionPlayPliabilityPositronPositron-Emission TomographyRadiationRadiation therapyRadiopharmaceuticalsRattusResearchResearch PersonnelResistanceResourcesRoleScanningSourceStaining methodStainsTechnologyThiosemicarbazonesUnited States National Institutes of Healthchemotherapycopper (II) diacetyl-di(N(4)-methylthiosemicarbazone)costresearch studyresponsestatisticstumoruptake
项目摘要
This subproject is one of many research subprojects utilizing the
resources provided by a Center grant funded by NIH/NCRR. The subproject and
investigator (PI) may have received primary funding from another NIH source,
and thus could be represented in other CRISP entries. The institution listed is
for the Center, which is not necessarily the institution for the investigator.
Tumor hypoxia has been an important prognositc factors because it limits the response to tumor treatment, such as resistance to radiation and chemotherapy. Positron emission tomography (PET) is a promising method to detect tumor hypoxia non-invasively.
However, this powerful modality is encumbered by the lack of available, approved radiopharmaceuticals. Proportional Technologies, Inc. (PTI) has developed a (62)Zn/(62)Cu generator that is capable of synthesizing (62)Cu bis(thiosemicarbazone) compounds, including (62)Cu-PTSM, a perfusion agent, and (62)Cu-ATSM, a hypoxia marker. The big advantage of the microgenerator is that it can practically deliver short lived radiopharmaceuticals with low cost and high flexibility. With the Cu-62 produced from microgenerator, we are able to perform the microPET study more easily and frequently. Other advantages of (62)Cu include a nearly 100% positron yield and a 9.7 minute half-life, which permits good image count statistics and serial studies.
In our previous study, we have evaluated (64)Cu-ATSM as a hypoxia imaging marker. We have found that perfusion plays an important role in hypoxia selectivity of Cu-ATSM, especially in those tumors with high perfusion level. In this study, we aim to conduct perfusion normalized hypoxia measurement using dual radiopharmaceuticals, (62)Cu-PTSM/(62)Cu-ATSM. Tumor hypoxia will be first imaged using (62)Cu-ATSM hypoxia
marker from microPET scanning. After the decay of (62)Cu-ATSM, (62)Cu-PTSM will be introduced to the same animal to obtain perfusion image, which will be used later to calculate perfusion normalized hypoxia. To verify the perfusion level in tumor, we will conduct microMRI scanning with contrast agent on the same animal after PET scanning. The hypoxia level will be also evaluated by dual autoradiography and hypoxia immunohistochemistry. Animal tumor radiation experiments will be conducted to correlate the hypoxia level measured from microPET and the response to radiation therapy.
The objectives of this study consist of the following:
1. To evaluate the feasibity of performing animal microPET study using 62Zn/62Cu microgenerator.
2. To evaluate the ability of (62)Cu-PTSM/(62)Cu-ATSM PET imaging to accurately reflect inter- and intra-tumoral hypoxia by comparing the distribution of uptake of (62)Cu-ATSM normalized by perfusion agent (62)Cu-PTSM with the distribution of EF5 hypoxia staining in 9L rat gliomas.
3. To evaluate the ability of (62)Cu-PTSM/(62)Cu-ATSM PET to predict individual tumor response to radiation therapy.
该子项目是利用该技术的众多研究子项目之一
资源由 NIH/NCRR 资助的中心拨款提供。子项目和
研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金,
因此可以在其他 CRISP 条目中表示。列出的机构是
对于中心来说,它不一定是研究者的机构。
肿瘤缺氧一直是一个重要的预后因素,因为它限制了肿瘤治疗的反应,例如对放射和化疗的抵抗。 正电子发射断层扫描(PET)是一种有前途的非侵入性检测肿瘤缺氧的方法。
然而,这种强大的方式因缺乏可用的、经批准的放射性药物而受到阻碍。 Proportional Technologies, Inc. (PTI) 开发了一种 (62)Zn/(62)Cu 发生器,能够合成 (62)Cu 双(缩氨基硫脲)化合物,包括灌注剂 (62)Cu-PTSM 和缺氧标记物 (62)Cu-ATSM。 微型发生器的一大优点是它实际上可以以低成本和高灵活性提供短寿命的放射性药物。借助微型发电机产生的 Cu-62,我们能够更轻松、更频繁地进行 microPET 研究。 (62)Cu 的其他优点包括近 100% 的正电子产率和 9.7 分钟的半衰期,这允许良好的图像计数统计和系列研究。
在我们之前的研究中,我们评估了 (64)Cu-ATSM 作为缺氧成像标记物。 我们发现灌注在 Cu-ATSM 的缺氧选择性中起着重要作用,特别是在那些具有高灌注水平的肿瘤中。在本研究中,我们的目标是使用双放射性药物(62)Cu-PTSM/(62)Cu-ATSM 进行灌注标准化缺氧测量。 首先使用 (62)Cu-ATSM 缺氧对肿瘤缺氧进行成像
microPET 扫描的标记。 (62)Cu-ATSM衰变后,将(62)Cu-PTSM引入同一动物以获得灌注图像,随后用于计算灌注归一化缺氧。为了验证肿瘤内的灌注水平,我们将在PET扫描后对同一动物进行使用造影剂的microMRI扫描。还将通过双重放射自显影和缺氧免疫组织化学评估缺氧水平。 将进行动物肿瘤放射实验,将 microPET 测量的缺氧水平与放射治疗的反应联系起来。
本研究的目标包括以下内容:
1. 评价利用62Zn/62Cu微型发电机进行动物microPET研究的可行性。
2. 通过比较9L大鼠胶质瘤中灌注剂(62)Cu-PTSM归一化的(62)Cu-ATSM摄取分布与EF5缺氧染色分布,评价(62)Cu-PTSM/(62)Cu-ATSM PET成像准确反映瘤间和瘤内缺氧的能力。
3.评估(62)Cu-PTSM/(62)Cu-ATSM PET预测个体肿瘤对放射治疗的反应的能力。
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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HONG YUAN的其他文献
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{{ truncateString('HONG YUAN', 18)}}的其他基金
COMPARISON HYPOXIA, GLUCOSE UPTAKE RAT R3230 TUMORS
比较缺氧、葡萄糖摄取大鼠 R3230 肿瘤
- 批准号:
7726115 - 财政年份:2008
- 资助金额:
$ 1万 - 项目类别:
COMPARISON HYPOXIA, GLUCOSE UPTAKE RAT R3230 TUMORS
比较缺氧、葡萄糖摄取大鼠 R3230 肿瘤
- 批准号:
7601137 - 财政年份:2007
- 资助金额:
$ 1万 - 项目类别:
COMPARISON HYPOXIA, GLUCOSE UPTAKE RAT R3230 TUMORS
比较缺氧、葡萄糖摄取大鼠 R3230 肿瘤
- 批准号:
7358260 - 财政年份:2006
- 资助金额:
$ 1万 - 项目类别:
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