Image-guided Diagnosis and Therapy of Neuroendocrine Tumors

神经内分泌肿瘤的影像引导诊断和治疗

基本信息

批准号：
8687491
负责人：
Yusuf Menda
金额：
$ 50.99万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-17 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8687491
关键词：
90Y Adult Affinity Algorithms Alternative Therapies Award Binding Caring Characteristics Chelating Agents Child Cities Clinical Clinical Trials Clinical Trials Network Cyclotrons Data Detection Development Diagnosis Diarrhea Discipline of Nuclear Medicine Dose Drug Formulations Drug resistance Early Diagnosis Effectiveness Excretory function FDA approved Family Flushing Future Gallium Image Imaging Techniques In 111 Pentetreotide Incidence Indium-111 Industry Iowa Kidney Kidney Neoplasms Label Lead Life Malignant Neoplasms Manufacturer Name Measurement Measures Medical center Metastatic Lesion Metastatic Neoplasm to the Liver Methods Molecular Molecular Target Neoplasm Metastasis Neuroendocrine Tumors Octreotide Operative Surgical Procedures Organ Patient Care Patient Monitoring Patient Selection Patients Pentetic Acid Peptide Receptor Pharmaceutical Preparations Pharmacologic Substance Positron Preparation Primary Lesion Procedures Production Progression-Free Survivals Protocols documentation Radiation Radiation therapy Radio Radioisotopes Radionuclide therapy Radiopharmaceuticals Regimen Relative (related person)Reporting Research Resolution Sensitivity and Specificity Societies Somatostatin Somatostatin Receptor Staging Survival Rate Symptoms Systemic Therapy Technology Testing Therapeutic Therapy Clinical Trials Time Toxic effect Translating Translations United States United States Department of Veterans Affairs Universities Variant Work X-Ray Computed Tomography base chemotherapy control trial cost effective cytotoxic design dosimetry evidence base image guided therapy improved industry partner innovation insight instrumentation meetings molecular imaging mortality neoplastic cell prospective receptor response standard of care tomography tumor uptake

项目摘要

DESCRIPTION (provided by applicant): Image-guided, molecularly-targeted peptide receptor radio-therapy (PRRT) provides superior response rates in patients with neuroendocrine tumors (NETs) compared to any treatments currently available; yet, it is not available for patients in the United States. Our proposal seeks to remedy this situation by developing standardized methods for [68Ga]DOTATOC PET/CT and for dosimetry-guided PRRT using [90Y]DOTATOC. INDs generated for initial clinical trials will be made freely available through the Society of Nuclear Medicine Clinical Trials Network, leading to submission of New Drug Applications (NDA) by our industry partners, Eckert-Zeigler (EZ) and Molecular Insight Pharmaceuticals (MIP). The end result will be to make [68Ga]DOTATOC PET/CT and [90Y]DOTATOC PRRT widely available in the US for patients with NETs. NET incidence has increased 5-fold over the last 30 years, but there is currently no curative treatment for the majority of these patients. Surgery can be curative in patients who are diagnosed early, but is limited by the fact that 80% of patients have inoperable metastases at diagnosis, with a 5-year survival rate <30%. Our preliminary data showing the first [68Ga]DOTATOC PET/CTs in the US, demonstrate superior imaging sensitivity and specificity compared to FDA approved Octreoscan for detection of primary and metastatic lesions. These findings strongly support our proposal to translate combined functional and anatomical imaging using [68Ga]DOTATOC PET/CT to the clinical arena for diagnosis, staging, and quantitative measurement of response to therapy in patients with NETs. 68Ga has advantages for clinical use because it can provide PET resolution without the need for a cyclotron; however, concerns about manufacturer ability to provide generator technology meeting regulatory compliance has slowed FDA acceptance in the US. Our strong preliminary data generated with GMP DOTATOC (MIP) and a gallium generator (EZ), demonstrate that [68Ga]DOTATOC can now be reliably prepared using disposable GMP compliant cassette-based kits (EZ), thereby making clinical [68Ga]DOTATOC possible within the framework of US regulatory requirements. No controlled trials have examined the potential of quantitative measurement of response to therapy using [68Ga]DOTATOC and no study has combined these efforts in a multisite prospective standardized trial that could advance these patient care regimens to widespread acceptance in the US. According to the definition of innovation in PAR-10-169, the proposed research is innovative because it develops an optimized and standardized proposal for image-guided PRRT using [68Ga]DOTATOC PET/CT for diagnosis, staging, and selection of patients that can benefit most from [90Y]DOTATOC therapy. This contribution is significant because it will identify the effects of radiopharmaceutical formulation characteristics on the relative effectiveness of the [68Ga]DOTATOC and [90Y]DOTATOC drug products, and will also result in a standardized platform to accelerate translation of PRRT to multi-institutiona clinical trials that will be required for widespread availability in the US. We know of no other Academic-Industry partnership that is capable of bringing [68Ga]DOTATOC PET/CT image-guided [90Y]DOTATOC therapy to the US for patients with NETs.

描述（由申请人提供）：与当前可用的任何治疗相比，图像引导的，分子靶向的肽受体放射治疗（PRRT）可为神经内分泌肿瘤（NETS）的患者提供较高的反应率；然而，它在患者中无法使用美国。我们的建议旨在通过开发[68GA] dotatoc PET/CT的标准化方法以及使用[90Y] dotatoc的剂量学引导的PRRT来纠正这种情况。将通过核医学协会临床试验网络免费提供用于初始临床试验的IND，从而导致我们的行业合作伙伴Eckert-Zeigler（EZ）和Molecular Insight Pharmaceuticals（MIP）提交新药应用（NDA）。最终结果是将[68GA] Dotatoc PET/CT和[90Y] Dotatoc Prrt在美国广泛使用，可用于网络患者。在过去的30年中，净发病率增加了5倍，但目前尚未针对这些患者的大多数治疗治疗。在早期诊断的患者中，手术可以治愈，但受到80％的患者在诊断时无法手术转移的限制，其存活率<30％。我们的初步数据显示了美国的第一个[68GA] dotatoc PET/CTS，与FDA批准的Octreoscan相比，表现出优异的成像敏感性和特异性，用于检测原发性和转移性病变。这些发现强烈支持我们使用[68GA] dotatoc PET/CT转化合并功能和解剖成像的建议，以诊断，分期和定量测量网络患者对治疗的反应。 68GA具有临床用途的优势，因为它可以提供宠物分辨率而无需回旋。但是，对制造商提供发电机技术会议法规合规性的关注使FDA在美国的接受程度放缓。我们使用GMP DoTATOC（MIP）和镀耐剂发电机（EZ）生成的强制初步数据，证明[68GA] DotAtoc现在可以使用符合GMP的GMP基于GMP的盒式盒子（EZ）可靠地制备，从而使临床[68GA] DotAtoc成为可能在美国监管要求的框架内。没有对照试验检查使用[68GA] DOTATOC对治疗反应进行定量测量的潜力，没有研究将这些努力结合在一起，将这些努力结合在一起，可以将这些患者护理方案推进到美国的广泛接受。根据PAR-10-169中的创新定义，该研究的研究具有创新性，因为它使用[68GA] DOTATOC PET/CT为诊断，分期和选择的患者提供了优化和标准化的建议，用于图像引导的PRRT。受益于[90Y] DOTATOC治疗。这种贡献很重要，因为它将确定放射性制剂特征的影响关于[68GA] DOTATOC和[90Y] DOTATOC药物的相对有效性，这也将导致标准化平台加速PRRT向多机构临床试验的翻译，这是美国广泛可用性所必需的。我们知道，没有其他能够为NETS患者带来[68GA] DOTATOC PET/CT图像引导[90Y] DOTATOTOC疗法的Dotatoc Pet/CT图像引导[90Y] DotatoT Therapy的学术合作伙伴关系。