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.

抽象的 基因药物的开发，例如嵌合抗原受体（CAR）等基因和细胞疗法 T 细胞需要新技术来监测这些疗法在人体中的生物分布 成像特别适合提供基因医学的定量测量。 随着时间的推移，Vellum Biosciences 是一家致力于填补这一技术空白的平台成像公司。 可重复、稳健、灵敏的原位遗传医学测量，在新药中具有明确的应用 Vellum 的技术的开发、临床研究和最终的临床实践都是基于正电子的。 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 当 DHFR 在基因传递药物中表达时（例如，二氢叶酸还原酶）。 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 该策略已用于监测 CAR T 细胞的运输。 在 STTR 第一阶段中，我们建议开发一种商业化的药物。 为 TMP 放射性示踪剂的广泛分布提供可行的放射合成途径 在 AIM1 中，我们将开发一种 两步放射合成工艺，可减少 HPLC 纯化的需要，并共同开发单一的 容器合成将适用于许多商业放射合成模块。在 AIM2 中，我们重点关注一个。 将这些短期目标放在一起，对放射化学产品进行基于盒的固相处理。 为 TMP 放射性示踪剂的商业放射性制药生产提供可行性和易处理性。 从广义上讲，成像预计在未来几十年中对于验证和优先考虑新的技术将特别重要 我们已经与全球制药公司建立了合作关系以使用基因医学疗法。 这些技术并设想这些方法对于下一代的进步至关重要 持续改善人类健康的药物。