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
• 负责人: Martin Gotthardt
• 金额: $ 14.57万
• 依托单位: RADBOUD UNIVERSITY NIJMEGEN MED CTR
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/7294222
• 关键词: Affect; Affinity; Age; Animal Model; Antibodies; Applications Grants; Area; B-Lymphocytes; Beta Cell; Binding; Biodistribution; Blood; Body Weight; Cell Transplantation; Cells; Central obesity; Control Groups; Cultured Cells; Defect; Development; Diabetes Mellitus; Discipline of Nuclear Medicine; Disease; Elderly; Enrollment; Functional disorder; GLP-I receptor; Gender; Human; Human body; Image; Insulin; Insulin-Dependent Diabetes Mellitus; Invasive; Iron; Islets of Langerhans Transplantation; Kinetics; Label; Magnetic Resonance Imaging; Measures; Methods; Monitor; Mus; Non-Insulin-Dependent Diabetes Mellitus; Numbers; Obesity; Oryctolagus cuniculus; Pancreas; Pathologic; Patients; Penetration; Peptides; Pilot Projects; Positron; Positron-Emission Tomography; Procedures; Purpose; Radioisotopes; Radiolabeled; Research; Research Personnel; Resolution; Rodent; Standards of Weights and Measures; Structure of beta Cell of islet; Techniques; Testing; Tissues; Tomography, Computed, Scanners; Tracer; X-Ray Computed Tomography; age group; analog; base; cellular imaging; diabetic; exenatide; glucagon-like peptide 1; healthy volunteer; helospectin I; in vivo; incretin hormone; interest; man; non-diabetic; pre-clinical; programs; radiotracer; receptor; research study; response; tool; uptake

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。