Kit for Instant Synthesis of 64Cu-ATSM

描述（由申请人提供）：正电子发射断层扫描（PET）是临床医生可用的众多诊断方案中的一种独特成像技术。与提供实体解剖特征成像的X射线、SPECT、CT、超声、MRI或乳房X线摄影术等技术不同，PET提供对被成像组织的代谢特征的单独聚焦。尽管PET成像在癌症的诊断、分期和疾病监测中提供了独特的信息，但由于缺乏批准的成像剂，该技术的更广泛使用受到阻碍。目前，只有一种单一的药物，18氟脱氧葡萄糖（18 F-FDG），被广泛用于PET成像研究。然而，铜的正电子发射同位素，例如62 Cu或64 Cu，是用于PET成像的有希望的放射性同位素，并且提供许多优点，包括与许多配体的简单配位化学，以允许在各种临床应用中使用。在这些专门的放射性药物化合物中，低氧特异性试剂64 Cu-ATSM已被证明优于其他低氧特异性成像剂。不幸的是，目前合成该化合物的方法对于多部位临床使用是不可行的，导致相当大的操作者辐射剂量，并产生不期望的基于乙醇的注射溶液。根据Proportional Technologies，Inc.的经验，(PTI)在用于合成Cu放射性药物的冻干试剂盒的制造中，我们建议将该技术扩展到开发与64 Cu相容的H2 ATSM试剂盒。这将通过扩展和调整PTI目前开发的用于62 Cu的H2 ATSM试剂盒的制造方法来实现，以克服寿命更长的64 Cu同位素所带来的技术挑战。该项目的主要焦点将是增加可用配体的浓度，以适应更高水平的放射性，同时保持合理的进样体积并保持配体溶解度。64 Cu-ATSM以适合于多部位临床使用的方式的可用性将补充18F-FDG用于肿瘤成像的使用，并扩展临床医生可用的PET成像剂的电池。开发一种用于肿瘤缺氧的稳健的、广泛可用的PET成像剂尤其重要，因为缺氧肿瘤通常对传统治疗方法具有抗性，并且通常与不良预后相关。通过使用64 Cu-ATSM尽早识别这种特征将有助于患者和医生诊断和管理疾病。公共卫生相关性：该项目涉及开发生产放射性药物化合物（放射性药物）64 Cu-ATSM的改进方法。这种放射性药物在进行正电子发射断层扫描（PET）成像扫描时使用，以识别肿瘤缺氧，并允许医生更有效地管理患者的治疗方案。

DESCRIPTION (provided by applicant): Positron Emission Tomography (PET) is a unique imaging technique among the many diagnostic protocols available to clinicians. Unlike techniques such as X-ray, SPECT, CT, ultrasound, MRI, or mammography that provide imaging of solid anatomical features, PET provides a solitary focus on the metabolic profile of the tissue being imaged. In spite of the unique information provided by PET imaging in the diagnosis, staging and disease monitoring of cancer, more widespread use of this technology is hampered by the dearth of approved imaging agents. Currently, only a single agent, 18F fluorodeoxyglucose (18F-FDG), is widely used for PET imaging studies. However, positron-emitting isotopes of copper, such as 62Cu or 64Cu, are promising radioisotopes for PET imaging and offer a number of advantages, including simple coordination chemistry with numerous ligands to allow use in a variety of clinical applications. Among these specialized radiopharmaceutical compounds is hypoxia-specific agent 64Cu-ATSM, which has demonstrated clear advantages over other hypoxia-specific imaging agents. Unfortunately, the current method of synthesizing this compound is not feasible for multi-site clinical use, results in considerable operator radiation dose, and gives an undesirable ethanol-based injection solution. Based on the experience of Proportional Technologies, Inc. (PTI) in the manufacture of lyophilized kits for synthesis of Cu radiopharmaceuticals, we propose that this technology be extended to the development an H2ATSM kit compatible for use with 64Cu. This will be accomplished through expansion and adaption of PTI's currently developed method of manufacturing H2ATSM kits for use with 62Cu to overcome the technical challenges presented by the longer-lived 64Cu isotope. The primary foci of the project will be increasing the concentration of available ligand to accommodate greater levels of radioactivity while preserving a reasonable injection volume and maintaining ligand solubility. The availability of 64Cu-ATSM in a manner appropriate for multi-site clinic use would supplement the use of 18F- FDG for imaging tumors and expand the battery of PET imaging agents available to the clinician. The development of a robust, widely-available PET imaging agent for tumor hypoxia is especially important since hypoxic tumors are generally resistant to traditional treatment methods and are often associated with poor prognosis. Identifying this trait as early as possible through the use of 64Cu-ATSM would assist patients and physicians in diagnosing and managing disease. PUBLIC HEALTH RELEVANCE: This project involves developing an improved means of manufacturing the radioactive pharmaceutical compound (radiopharmaceutical) 64Cu-ATSM. This radiopharmaceutical is used when conducting Positron Emission Tomography (PET) imaging scans to identify tumor hypoxia and allow physicians to more effectively manage a patient's treatment options.