I-Corps: Radiotracer Synthesis Commercialization

拟议的I-Corps项目涉及将[18F]标记的分子成像剂合成的有利新方法引入临床。拟议的活动建立在合成化学的基础发现上，这些发现是由先前的NSF资助实现的。在目前的项目中，该团队评估了新开发和演示的技术是否适合作为组建初创企业的基础。在6个月的资助期内将开展的活动包括市场评估、围绕这些发明的知识产权评估以及与潜在客户、被许可方和竞争对手的广泛直接接触。这些活动将由I-Corps计划的课程指导和通知。正电子发射断层扫描（PET）是一种功能强大的非侵入性诊断分子成像技术。对于大多数PET应用，[18F]氟化放射性示踪剂是优选的。这种氟同位素的半衰期较短（约110分钟），需要在显著的时间限制下制备和分配相对复杂的化合物，同时仍提供优异的图像质量、符合FDA良好制造规范以及短半衰期放射性核素典型的可接受的放射剂量测定。一种这样的化合物，[18 F]-2-氟-2-脱氧葡萄糖（FDG），现在占据了几乎所有的[18 F]-PET成像市场，在美国估计约为5亿美元/年，并为癌症患者的临床管理提供了重要的支持。实验室开发的独特技术将允许快速有效地生产额外的非常高比活度的氟化PET化合物，其临床使用受到当前放射化学合成方法的限制。在该项目中将推进的新技术为合成[18F]标记的成像剂提供了商业上兼容的合成途径和新的化学中间体，这些成像剂可用于评估大脑和心脏中特定细胞受体的病理生理学，定位和分期肿瘤，并通过监测患者对治疗的反应来协助癌症管理。

The proposed I-Corps project involves bringing advantageous new methodologies for synthesis of [18F]-labeled molecular imaging agents into the clinic. The proposed activity builds upon fundamental discoveries in synthetic chemistry that were made possible by prior NSF funding. In the current project the team assesses the suitability of newly developed and demonstrated technology as the basis for forming a startup enterprise. Activities to be performed during the 6 month funding period will include market assessment, evaluation of the intellectual property surrounding these inventions, and extensive direct contacts with potential customers, licensees, and competitors. These activities will be guided and informed by the curriculum of the I-Corps program. Positron Emission Tomography (PET) is a powerful, noninvasive diagnostic molecular imaging technique. For most PET applications, [18F]fluorinated radiotracers are preferred. The short half-life of this isotope of fluorine (~110 min) requires relatively complex compounds to be prepared and distributed under significant time constraints, while still providing the excellent image quality, compliance with FDA good manufacturing practices, and acceptable radiodosimetry typical of short half-life radionuclides. One such compound, [18F]- 2-fluoro-2-deoxyglucose (FDG), now accounts for the almost all of the [18F]-PET imaging market, estimated to be approximately $500MM/yr in the United States and provides significant support for the clinical management of cancer patients. Unique technology developed in the laboratory will permit rapid and efficient production of additional very high specific activity fluorinated PET compounds for which clinical use has been constrained by the limitations of current radiochemical synthesis methods. The new technology to be advanced in this project provides commercially compatible synthetic pathways and new chemical intermediates for the synthesis of [18F]-labeled imaging agents that can be used to evaluate the pathophysiology of specific cellular receptors in the brain and in the heart, to localize and stage tumors, and to assist in cancer management by monitoring patients' responses to therapy.