TARGETED 99M TC RADIOPHARMACEUTICAL FOR TUMOR IMAGING

这项第一阶段SBIR赠款的目标是推动 一种新型的基于~(99m)Tm的放射性药物--99mTc-HYNIC-叶酸，As 一种肿瘤靶向显像剂。使用以下工具有几个优点 99mTc作为放射性核素用于成像，包括成本、可获得性和 短暂的半衰期。~(99m)Tc成功掺入叶酸- 靶向系统应该能够开发出诊断肿瘤的成像 这款产品可以同时提高图像质量和灵敏度，同时降低 病人暴露在辐射中的代价是其他人的一小部分. 市场上可买到的肿瘤特异性显像剂。具体目标 本研究主要研究内容如下：L)建立使用的最佳条件 用于大规模合成和提纯亚叶酸，2)至 建立一种可靠的制备和纯化99mTc-羟基叶酸的方法，3) 进行体外细胞摄取研究，以验证99mTc- HYNIC-叶酸为叶酸受体，以及4)进行初步动物实验 成像和生物分布研究。在这些项目完成后 具体目标，将启动一个第二阶段项目，其中包括 向国际标准化组织提交99mTC-HYNIC-叶酸的公司申请 FDA和LND I/II期临床研究的启动 密苏里州圣路易斯市的华盛顿大学医学中心。 建议的商业应用： 拟议的项目旨在将~(99m)Tc-羟基叶酸开发成 临床放射性药物产品将用于核素照相 肿瘤的诊断成像。该产品可能会显著影响 通过为某些癌症患者提供快速和 高灵敏度的肿瘤检测方法。

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.