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的独特成像技术。与X射线，SPECT，CT，超声，MRI或乳房X线摄影等技术不同，PET可以单独关注正在成像的组织的代谢谱。尽管PET成像在诊断，分期和疾病监测癌症中提供的独特信息，但对该技术的更广泛使用受到批准成像剂的缺乏的阻碍。当前，只有一种单一的药物，即18F氟脱氧葡萄糖（18F-FDG），被广泛用于宠物成像研究。但是，铜的正电子发射同位素，例如62cu或64cu，是有望用于PET成像的放射性同位素，并提供了许多优势，包括简单的配位化学和许多配体可以允许在各种临床应用中使用。在这些专门的放射药物化合物中，有缺氧特异性剂64cu-ATSM，它与其他低氧特异性成像剂相比具有明显的优势。不幸的是，当前合成该化合物的方法对于多站点的临床使用不可行，导致相当大的载剂辐射剂量，并提供了不良的基于乙醇的注射溶液。根据比例技术的经验，Inc。（PTI）在合成Cu radiopharmaceuticals合成的冻干试剂套件中生产的经验，我们建议将该技术扩展到与64CU一起使用的H2ATSM套件兼容的开发。这将通过扩展和适应PTI当前开发的制造H2ATSM套件的方法来实现，以与62CU一起使用，以克服寿命长的64CU同位素提出的技术挑战。该项目的主要焦点将增加可用配体的浓度，以适应更高水平的放射性，同时保留合理的注射量并保持配体溶解度。 64CU-ATM的可用性以适用于多站点诊所使用的方式，可以补充18F-FDG进行成像肿瘤的使用，并扩大临床医生可用的PET成像剂的电池。由于缺氧肿瘤通常对传统治疗方法具有抵抗力，并且通常与预后不良有关，因此肿瘤缺氧的强大，广泛可用的宠物成像剂的发展尤为重要。通过使用64CU-ATM尽早确定这一特征将帮助患者和医生诊断和管理疾病。公共卫生相关性：该项目涉及开发改进的放射性药物化合物（放射性药物）64CU-ATSM的方法。进行正电子发射断层扫描（PET）成像扫描以鉴定肿瘤缺氧并使医生能够更有效地管理患者的治疗方案时，使用这种放射性药物。