Optimizing the synthesis of[18F]FTMP for commercial distribution

优化 [18F]FTMP 的合成以进行商业分销

• 批准号: 10601199
• 负责人: Mark A Sellmyer
• 金额: $ 29.99万
• 依托单位: VELLUM BIOSCIENCES LLC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-15 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10601199
• 关键词: Address; Adenovirus Vector; Animals; Antibiotics; Area; Biodistribution; Biological Sciences; Biopsy; Cell Therapy; Cells; Chemistry; Clinical; Clinical Management; Clinical Protocols; Clinical Research; Consumption; Data; Development; Dihydrofolate Reductase; Disadvantaged; Drug Kinetics; Engineering; Escherichia coli; Fluorine; Genes; Genetic Medicine; Goals; Grant; HSV-Tk Gene; Health; High Pressure Liquid Chromatography; Human; Image; Immune; In Situ; Label; Lentivirus Vector; Letters; Literature; Location; Measurement; Measures; Medicine; Messenger RNA; Methods; Monitor; Multi-Institutional Clinical Trial; Multicenter Trials; Pathologic; Patients; Pennsylvania; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phase II/III Clinical Trial; Positron-Emission Tomography; Principal Investigator; Process; Production; Proteins; Publishing Peer Reviews; Radiolabeled; Radiopharmaceuticals; Reaction; Reporter; Reporter Genes; Research; Research Personnel; Rodent; Route; Running; Site; Small Business Innovation Research Grant; Small Business Technology Transfer Research; Solid; Solid Neoplasm; Sterility; System; Technology; Testing; Time; Tissues; Toxic effect; Training; Trimethoprim; Universities; Work; analog; chimeric antigen receptor T cells; clinical practice; clinical translation; commercialization; drug development; feasibility testing; first-in-human; gene therapy; imaging agent; imaging biomarker; imaging modality; imaging platform; improved; in vivo; molecular imaging; new technology; next generation; novel therapeutics; pre-clinical; predicting response; programs; protein expression; quantitative imaging; radiochemical; radiotracer; research and development; small molecule; targeted imaging; technology platform; therapeutic biomarker; trafficking; uptake

Abstract The development of genetic medicines such as gene and cell therapies like Chimeric Antigen Receptor (CAR) T cells has necessitated new technologies that can monitor the biodistribution of these therapies in human patients. Imaging is particularly well suited to provide such quantitative measurements of a genetic medicine over time. Vellum Biosciences is a platform imaging company geared to fill this void in technology, providing repeatable, robust, sensitive measures of a genetic medicine in situ with clear applications in new drug development, clinical research, and eventually clinical practice. Vellum’s technology is based on positron emission tomography (PET) radiotracer derivatives of the synthetic antibiotic trimethoprim (TMP) and its protein target dihydrofolate reductase (DHFR). When DHFR is expressed in a genetically delivered medicine (e.g. mRNA, lentiviral or adenoviral vectors), TMP radiotracers can be used to measure the expression of the protein products in any tissue within the body. This strategy has been used to monitor the trafficking of CAR T cells targeting several solid tumors in animals. In this STTR phase 1, we propose the development of a commercially viable radiosynthetic route for broad, widespread distribution of TMP radiotracers. In AIM1, we will develop a two-step radiosynthetic process which shall decrease the need for HPLC purification and co-develop a single vessel synthesis which will be applicable to many commercial radiosynthesis modules. In AIM2, we focus on a cartridge-based, solid-phase workup of the radiochemical products. Taken together these short-term goals provide both the feasibility and tractability for commercial radiopharmacy production of TMP radiotracers. More broadly, imaging is expected to be particularly important in the coming decades to validate and prioritize new genetic medicine therapies. We have already formed relationships with global pharmaceutical companies to use these technologies and envision that these approaches are critical to the advancement of next-generation medicines for the continued improvement of human health.

摘要 基因药物的发展，如基因和细胞疗法，如嵌合抗原受体（CAR） T细胞需要新的技术，可以监测这些疗法在人体内的生物分布 患者成像特别适合于提供遗传医学的这种定量测量 随着时间Vellum Biosciences是一家平台成像公司，旨在填补技术空白， 可重复的、稳健的、灵敏的原位遗传药物测量，在新药开发中具有明确的应用 发展，临床研究，最终临床实践。Vellum的技术是基于正电子 合成抗生素甲氧苄啶（TMP）及其蛋白质的发射断层扫描（PET）放射性示踪剂衍生物 靶向二氢叶酸还原酶（DHFR）。当DHFR在基因递送的药物中表达时（例如， mRNA、慢病毒或腺病毒载体），TMP放射性示踪剂可用于测量蛋白质的表达 产品在体内的任何组织。该策略已用于监测CAR T细胞的运输 靶向动物体内的几种实体瘤。在这个STTR第1阶段，我们建议开发一种商业化的 TMP放射性示踪剂广泛分布的可行的放射性合成途径。在AIM1中，我们将开发一个 两步放射合成工艺，这将减少对HPLC纯化的需求，并共同开发单一的 容器合成，其将适用于许多商业放射合成模块。在AIM2中，我们专注于 放射化学产物的固相后处理。把这些短期目标放在一起 为TMP放射性示踪剂的商业放射性药物生产提供了可行性和易处理性。更 总的来说，在未来几十年中，成像预计将特别重要，以验证和优先考虑新的 基因医学疗法我们已经与全球制药公司建立了关系， 这些技术，并设想这些方法是至关重要的下一代的进步， 药物，以持续改善人类健康。