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

摘要 基因药物和嵌合抗原受体(CAR)等细胞疗法的研究进展 T细胞需要新的技术来监测这些疗法在人类体内的生物分布 病人。成像特别适合于提供这样的基因药物的定量测量。 随着时间的推移。Vellum Biosciences是一家平台成像公司，旨在填补这一技术空白，提供 一种可重复、可靠、灵敏的原位遗传药物测量方法，在新药中有明确的应用 开发、临床研究和最终的临床实践。维勒姆的技术是基于正电子的 合成抗生素甲氧苄氨嘧啶(TMP)及其蛋白的PET放射性示踪衍生物 靶二氢叶酸还原酶(DHFR)。当dhfr在基因药物中表达时(例如 M RNA、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 体内任何组织中的产品。这一策略已被用于监测CAR T细胞的贩运 靶向动物体内的几个实体肿瘤。在本STTR第1阶段中，我们建议开发一种商用的 广泛、广泛分布TMP放射性示踪剂的可行放射合成路线。在AIM1中，我们将开发一种 两步放射合成工艺，将减少对高效液相纯化的需要，并共同开发单一的 将适用于许多商业放射合成模块的容器合成。在AIM2中，我们关注一个 以药筒为基础的放射化学产品的固相处理。把这些短期目标放在一起 为TMP放射性示踪剂的商业化生产提供了可行性和可操作性。更多 总的来说，在未来几十年中，成像对于验证和确定新技术的优先顺序尤其重要 基因药物疗法。我们已经与全球制药公司建立了合作关系，以使用 这些技术和设想这些方法对下一代的发展至关重要 持续改善人类健康的药物。

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.