SBIR-STTR Award

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

This phase Il application is part of a program to commercialize a folate targeted diagnostic imaging agent. Endocyte has developed and is conducting clinical trials with a folate targeted Indium-I Il agent (111In- DTPA-folate). The objective of this Phase Il SBlR grant is to complete pre-clinical development, file an IND, and conduct a phase I/II clinical trial with a folate targeted technetium diagnostic agent (99mTc-EC14). A 99mTc based folate-targeted system has many advantages over an Indium based agent including improved image quality, lower cost, and reduced radiation exposure. The specific aims for this study are as follows: 1. To perform pre-clinical pharmacology studies aimed at determining 99mTc-EC14's biodistribution, pharmacokinetic, and serum protein binding properties; and metabolic fate; 2. To conduct an "Expanded Acute Toxicity Study" in two animal species; 3. To generate 99mTc-EC14 radiopharmaceutical kits manufactured and packaged in accordance with cGMP requirements for use in human clinical trials; 4. To prepare and submit an IND application to the FDA to obtain approval for the initiation of a Phase I/II human clinical trial. 5. To conduct a Phase I/II clinical study in ovarian cancer patients to evaluate the safety and efficacy of the 99mTc-ECI4 product for imaging primary and metastatic ovarian carcinomas. PROPOSED COMMERCIAL APPLICATIONS: The proposed project is aimed at developing a Tc99m-folate imaging agent to be used in diagnoses of malignant tumors expressing the folate receptor. This product will significantly impact clinical management of an estimated 300,000 folate receptor positive cancer patients by providing a safe, affordable, and accurate method to distinguish between malignant and benign masses, locate metastatic sites, check for recurrence, and identity cancers for folate targeted therapy