TARGETED 99M TC RADIOPHARMACEUTICAL FOR TUMOR IMAGING

第一阶段SBIR赠款的目的是促进以下方面的发展： 一种新的基于锝99 m的放射性药物，99 mTc-HYNIC-folate， 一种肿瘤靶向显像剂。有几个优点，使用 99 mTc作为放射性核素用于成像，包括成本、可用性和 半衰期短。成功地将99 mTc掺入叶酸- 靶向系统应该能够开发诊断肿瘤成像 产品可以提高图像质量和灵敏度，同时减少 病人暴露在辐射中的费用是其他费用的一小部分， 市售的肿瘤特异性成像剂。具体目标 本研究的主要内容如下：1）建立了最佳的实验条件 对于HYNIC-叶酸的大规模合成和纯化，2） 建立了一种可靠的制备和纯化99 mTc-HYNIC-叶酸的方法，3） 进行体外细胞摄取研究，以验证99 mTc的特异性- HYNIC-叶酸受体的叶酸，和4）进行初始动物 成像和生物分布研究。在完成这些 为了实现具体目标，将启动一个第二阶段项目， 提交了一份99 mTc-HYNIC-叶酸的公司IND申请， FDA和在2015年启动的IND I/II期临床研究 密苏里州圣路易斯市的华盛顿大学医学中心。 拟定商业应用： 拟议的项目旨在将Tc-99 m-HYNIC-叶酸开发成一种 放射性造影中使用的临床放射性药物产品 肿瘤的诊断成像。 该产品可能会严重影响 通过提供一种快速和有效的方法， 高灵敏度肿瘤检测方法。

The objective of this Phase I SBIR grant is to advance the development of a novel Technetium 99m-based radiopharmaceutical, 99mTc-HYNIC-folate, as a tumor-targeted imaging agent. There are several advantages to using 99mTc as a radionuclide for imaging including cost, availability, and short half life. The successful incorporation of 99mTc into a folate- targeted system should enable development of a diagnostic tumor imaging product that can improve both image quality and sensitivity while reducing a patient's exposure to radiation at a fraction of the cost of other commercially available tumor-specific Imaging agents. The specific aims for this study are as follows: l) to establish the optimal conditions used for the large scale synthesis and purification of HYNIC-folate, 2) to develop a reliable method to prepare and purify 99mTc-HYNIC-folate, 3) to conduct in vitro cell uptake studies to verify the specificity of 99mTc- HYNIC-folate for the folate receptor, and 4) to conduct initial animal imaging and biodistribution studies. Following the completion of these specific aims, a phase II project will be initiated which includes the submission of a corporate IND application for 99mTc-HYNIC-folate to the FDA and the initiation of a lND Phase I/II clinical study at the Washington University Medical Center in St. Louis, MO. PROPOSED COMMERCIAL APPLICATION: The proposed project is aimed at developing Tc-99m-HYNIC-folate into a clinical radiopharmaceutical product to be used in the scintigraphic diagnostic imaging of tumors. This product may significantly impact the clinical management of certain cancer patients by providing a rapid and highly sensitive method of tumor detection.