Non-invasive beta-cell imaging using a Ga-68-labeled glucagone-like peptide-1 ana
使用 Ga-68 标记的胰高血糖素样肽 1 ana 进行非侵入性 β 细胞成像
基本信息
- 批准号:7224577
- 负责人:
- 金额:$ 15万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-09-30 至 2009-08-31
- 项目状态:已结题
- 来源:
- 关键词:bioimaging /biomedical imagingbiological modelsclinical researchcomputed axial tomographydisease /disorder modelgalliumhuman subjectinsulin dependent diabetes mellituslaboratory mouselaboratory rabbitmolecular /cellular imagingnoninsulin dependent diabetes mellituspancreatic islet transplantationpancreatic isletspatient oriented researchpharmacokineticspositron emission tomographyradiation dosageradionuclidesradiotracertechnology /technique developmenttissue /cell culture
项目摘要
DESCRIPTION (provided by applicant):
The function of pancreatic beta-cell cells is a key issue in diabetes mellitus, but can only be assessed indirectly. Currently, several aspects regarding beta-cell mass remain to be elucidated, for example: (1) Is the total beta-cell mass at the onset of type 2 diabetes diminished or not, (2) how does the beta-cell mass develop during the course of the disease, (3) which factors affect beta-cell mass, and (4) how does beta-cell mass relate to the response to therapy. Futhermore, it would be of great interest to measure beta-cell mass after islet-transplantation. Research is hampered by the fact that no reliable methods exist to assess and quantify human beta-cell mass in vivo. If beta-cell mass could be determined by a non-invasive method, this would be of a tremendous asset in advancing this field of research.
We have developed a radiolabeled agent (DOTA-Lys40-Exendin 4) that allows specific beta-cell imaging. In mice the tracer shows uptake of approximately 9% of the injected activity per gram of pancreas tissue. This specific tracer is therefore a promising tool for in vivo beta-cell imaging in humans.Under this grant proposal, we will develop a Ga-68 labeled DOTA-Exendin compound for imaging of beta-cells in vivo with positron emission tomography (PET). The use of a positron emitter such as Ga-68 will offer a number of advantages over conventional nuclear medicine imaging: 1. high spatial resolution, 2. accurate quantification, 3. exact localization of the pancreas / the beta-cell areas by use of an integrated PET/CT scanner (CT=computed tomography), even if pancreatic tracer uptake is decreased after beta-cell loss. In comparison to Magnetic Resonance Imaging (MRI), the approach is very sensitive and will not require direct labeling of beta-cells for imaging purposes. Direct labeling (for example with iron) can only be done in beta-cell transplantation (prior to islet transplantation) but is not suitable for imaging of pancreatic beta-cells in vivo.
In this project, we will investigate the correlation of uptake of the Ga-68-labeled DOTA-Exendin and beta-cell mass in different animal models of diabetes. Upon succesful pre-clinical development of the tracer, pilot studies in humans will be conducted. Apart from proof-of-principle studies in healthy volunteers and diabetes type I and II patients, a dosimetric method will be established to simply and reliably quantify beta-cell mass by PET imaging.
描述(由申请人提供):
胰腺β细胞细胞的功能是糖尿病中的关键问题,但只能间接评估。目前,有关β细胞质量的几个方面仍有待阐明,例如:(1)是在2型糖尿病发作时的总β细胞质量减少,(2)β细胞质量在疾病过程中如何发展,(3)哪些因素哪些因素影响β细胞质量,以及(4)(4)(4)beta-cell质量与响应如何相关的响应。 futhermore,在胰岛转移后测量β细胞质量会引起极大的兴趣。没有可靠的方法来评估和量化体内人类β细胞质量的事实,这一事实受到了阻碍。如果可以通过非侵入性方法确定β细胞质量,那么这将是巨大的资产,在推进这一研究领域。
我们已经开发了一种放射性标记的剂(DOTA-LYS40-EXENDIN 4),该剂允许特定的β细胞成像。在小鼠中,示踪剂显示每克组织注射活性的9%。因此,这种特定的示踪剂是人类体内β细胞成像的有前途的工具。在此赠款建议下,我们将开发一个标记为DOTA-Exendin化合物的GA-68,用于使用Potitron发射层析成像(PET)的体内β细胞成像。 The use of a positron emitter such as Ga-68 will offer a number of advantages over conventional nuclear medicine imaging: 1. high spatial resolution, 2. accurate quantification, 3. exact localization of the pancreas / the beta-cell areas by use of an integrated PET/CT scanner (CT=computed tomography), even if pancreatic tracer uptake is decreased after beta-cell loss.与磁共振成像(MRI)相比,该方法非常敏感,并且不需要直接标记β细胞的成像目的。直接标记(例如铁)只能在β细胞移植(胰岛移植之前)进行,但不适用于体内胰腺β细胞的成像。
在这个项目中,我们将研究不同动物糖尿病动物模型中GA-68标记的Dota-exendin和β细胞质量的摄取的相关性。随着示踪剂的成功临床前发展,将对人类进行试点研究。除了对健康志愿者和I型糖尿病和II患者进行原则研究证明,还将建立一种剂量学方法,以简单而可靠地通过PET成像量化β细胞质量。
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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Martin Gotthardt其他文献
Martin Gotthardt的其他文献
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{{ truncateString('Martin Gotthardt', 18)}}的其他基金
Non-invasive beta-cell imaging using a Ga-68-labeled glucagone-like peptide-1 ana
使用 Ga-68 标记的胰高血糖素样肽 1 ana 进行非侵入性 β 细胞成像
- 批准号:
7294222 - 财政年份:2006
- 资助金额:
$ 15万 - 项目类别:
Non-invasive beta-cell imaging using a Ga-68-labeled glucagone-like peptide-1 ana
使用 Ga-68 标记的胰高血糖素样肽 1 ana 进行非侵入性 β 细胞成像
- 批准号:
7479608 - 财政年份:2006
- 资助金额:
$ 15万 - 项目类别:
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