Kit for Instant Synthesis of 64Cu-ATSM

64Cu-ATSM 即时合成试剂盒

• 批准号: 7538298
• 负责人: JEFFREY L LACY
• 金额: $ 13.14万
• 依托单位: PROPORTIONAL TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7538298
• 关键词: Achievement; Address; Animals; Biodistribution; Brain imaging; Buffers; Cardiology; Chemistry; Clinic; Clinical Investigator; Clinical Trials; Compatible; Condition; Copper; Development; Diagnosis; Diagnostic; Disease; Dose; Drug Formulations; Ethanol; Freeze Drying; Goals; Guanosine Monophosphate; Hypoxia; Image; Imaging Techniques; Individual; Injection of therapeutic agent; Isotonic Solutions; Isotopes; Life; Ligands; Lung; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Mammography; Marketing; Metabolic; Methods; Monitor; Multi-Institutional Clinical Trial; Myocardial perfusion; Numbers; Patients; Perfusion; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Physicians; Positron; Positron-Emission Tomography; Preparation; Production; Protocols documentation; Public Health; Pyrogens; Radiation; Radioactive; Radioactivity; Radioisotopes; Radiopharmaceuticals; Resistance; Roentgen Rays; Sampling; Scanning; Serum; Simulate; Site; Solid; Solubility; Solutions; Solvents; Staging; Stem Cell Factor; Sterility; Sucrose; Techniques; Technology; Temperature; Testing; Thiosemicarbazones; Tissues; Training; Ultrasonography; United States Food and Drug Administration; Universities; Vendor; Vial device; Washington; Work; base; cancer type; clinical application; clinical research site; day; experience; fluorodeoxyglucose; improved; interest; laboratory facility; novel; oncology; outcome forecast; pre-clinical; prognostic; radiochemical; reconstitution; research and development; response; single photon emission computed tomography; size; trait; tumor

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.

描述（由申请人提供）：正电子发射断层扫描（PET）是临床医生可用的许多诊断方案中独特的成像技术。与x射线、SPECT、CT、超声、MRI或乳房x线摄影等技术提供实体解剖特征的成像不同，PET提供了对被成像组织代谢谱的单独关注。尽管PET成像在癌症的诊断、分期和疾病监测方面提供了独特的信息，但由于缺乏经批准的显像剂，这项技术的更广泛应用受到了阻碍。目前，只有18F氟脱氧葡萄糖（18F- fdg）这一单一试剂被广泛用于PET成像研究。然而，铜的正电子发射同位素，如62Cu或64Cu，是很有希望用于PET成像的放射性同位素，并提供了许多优点，包括与许多配体进行简单的配位化学反应，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，低氧特异性剂64Cu-ATSM已被证明比其他低氧特异性显像剂具有明显的优势。不幸的是，目前合成该化合物的方法不适合多部位临床使用，导致相当大的操作员辐射剂量，并且给出了不理想的乙醇基注射溶液。基于Proportional Technologies， Inc. （PTI）在生产用于合成Cu放射性药物的冻干试剂盒方面的经验，我们建议将该技术扩展到开发与64Cu兼容的H2ATSM试剂盒。这将通过扩展和适应PTI目前开发的用于62Cu的H2ATSM套件的制造方法来实现，以克服长寿命64Cu同位素带来的技术挑战。该项目的主要重点将是增加可用配体的浓度，以适应更高水平的放射性，同时保持合理的注射量和保持配体的溶解度。64Cu-ATSM以一种适合多地点临床使用的方式可用，将补充18F- FDG用于肿瘤成像的使用，并扩大临床医生可用的PET显像剂系列。由于缺氧肿瘤通常对传统治疗方法有抵抗性，且通常伴有预后不良，因此开发一种强大的、广泛可用的肿瘤缺氧PET显像剂尤为重要。通过使用64Cu-ATSM尽早识别这一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：该项目涉及开发一种改进的生产放射性药物化合物（放射性药物）64Cu-ATSM的方法。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。