Preparation of a Quantitative Apoptosis Imaging Agent

这项建议致力于开发新的成像技术，以无创地定量测量体内的细胞凋亡。细胞凋亡是基因上定义的细胞死亡。了解细胞凋亡的作用对于开发新的基于分子的治疗方式至关重要。一种细胞凋亡显像剂可以用来改进癌症患者的治疗方法，并监测心脏移植患者。我们的团队目前正在参与一项细胞凋亡成像试验，使用了Technedium-99m标记的Annexin-V。我们建议用适合于PET扫描的正电子发射体标记Annexin-V。PET的潜在优势包括改进的空间分辨率和定量，这对于监测早期癌症和心脏研究将是重要的。第一阶段的研究将包括开发Annexin-V的有效放射性氟化程序。第一阶段的主要目标是：(1)达到业界公认的有用的PET显像剂的参数(即比活性和较短的制备时间)，以及(2)在经典的细胞凋亡模型中展示体外结合活性。进一步的第一阶段工作是评估化疗后的儿科肿瘤细胞培养物中的生物活性，这将为后续的动物试验奠定基础。这些后续研究将使用PEM技术公司专有的PET引导活检工具。拟议的商业应用：PET放射性示踪剂的开发是一个高增长领域，每年用于新的生产和研发的投资超过1.5亿美元。这项建议的产品将有助于对基于分子的抗癌剂的疗效进行非侵入性定量测量。提议的公司(PEM Technologies)提供具有成本效益的PET成像和PET引导活检的专有平台。

This proposal addresses development of new imaging technology for noninvasive quantitative measurement of apoptosis in vivo. Apoptosis is genetically defined cell death. Understanding the role of apoptosis is critical to the development of new molecular-based therapeutic modalities. An apoptosis-imaging agent could be used to modify therapy for cancer patients, and to monitor cardiac transplant patients. Our group is currently participating in an apoptosis imaging trial, employing Annexin-V labeled with Technetium-99m. We propose to label Annexin-V with a positron emitter appropriate for PET scanning. Potential advantages of PET include improved spatial resolution and quantitation, which will be important for monitoring early cancers and for cardiac studies. Phase I research will consist of development of a procedure for effective radiofluorination of Annexin-V. The main goals of Phase I are: (1) the attainment of parameters (i.e., specific activity, and short preparation time) accepted in the industry as requirements for a useful PET imaging agent, and (2) demonstration of in vitro binding activity in classic models for apoptosis. Further Phase I work to assess biologic activity in chemotherapy-treated cultures of pediatric tumor cells will set the stage for subsequent animal testing. These later studies will employ PEM Technologies' proprietary PET-guided biopsy tools. PROPOSED COMMERCIAL APPLICATIONS: Development of radiotracers for PET is a high-growth area, with over $150 million invested annually for new production and R&D. The product of this proposal will aid noninvasive quantitative measurements as to the efficacy of molecular-based anticancer agents. The proposing company (PEM Technologies) offers proprietary platforms for cost-effective PET imaging and PET-guided biopsy.