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) 是临床医生可用的众多诊断方案中的一种独特的成像技术。与提供实体解剖特征成像的 X 射线、SPECT、CT、超声、MRI 或乳房 X 线照相术等技术不同，PET 只关注被成像组织的代谢特征。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，该技术的更广泛使用受到阻碍。目前，只有一种药物 18F 氟脱氧葡萄糖 (18F-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 62Cu 或 64Cu）是用于 PET 成像的有前景的放射性同位素，并具有许多优点，包括与大量配体的简单配位化学，可用于各种临床应用。在这些专门的放射性药物化合物中，缺氧特异性试剂 64Cu-ATSM 与其他缺氧特异性显像剂相比具有明显的优势。不幸的是，目前合成该化合物的方法对于多部位临床使用来说是不可行的，导致相当大的操作者​​辐射剂量，并且产生不期望的基于乙醇的注射溶液。基于Proportional Technologies, Inc. (PTI)在制造用于合成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。这将通过扩展和调整 PTI 目前开发的用于 62Cu 的 H2ATSM 套件制造方法来实现，以克服寿命较长的 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并维持配体溶解度。 64Cu-ATSM 以适合多站点临床使用的方式提供，将补充 18F-FDG 在肿瘤成像中的使用，并扩大临床医生可用的 PET 成像剂的范围。开发一种强大的、广泛使用的 PET 成像剂来治疗肿瘤缺氧尤为重要，因为缺氧肿瘤通常对传统治疗方法有抵抗力，并且通常与不良预后相关。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。公共健康相关性：该项目涉及开发一种改进的放射性药物化合物（放射性药物）64Cu-ATSM 的制造方法。这种放射性药物用于进行正电子发射断层扫描 (PET) 成像扫描，以识别肿瘤缺氧情况，并使医生能够更有效地管理患者的治疗选择。