A kit based PET agent: edotreotide Ga 68 for clinical imaging of somatostatin rec

基于试剂盒的 PET 试剂：edotreotide Ga 68，用于生长抑素临床成像

基本信息

批准号：
8315099
负责人：
JAMES F KRONAUGE
金额：
$ 54.21万
依托单位：
MOLECULAR INSIGHT PHARMACEUTICALS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-17 至 2013-04-22
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8315099
关键词：
Award Binding Biological Biological Markers Carcinoid Tumor Cell Culture Techniques Chemistry Clinical Clinical Protocols Clinical Research Clinical Trials Clinical Trials Network Collaborations Communities Data Databases Development Diagnostic Diagnostic Imaging Documentation Dose Drug Formulations Equipment and supply inventories Evaluation Freeze Drying Gallium Gastrinoma General Hospitals Generations Generic Drugs Genomics Goals Growth Factor Hormones Human Image In 111 Pentetreotide In Vitro Indium-111 Industry Institution Institutional Review Boards Isotopes Kinetics Label Licensing Life Malignant - descriptor Malignant Neoplasms Malignant neoplasm of prostate Massachusetts Medicine Molecular Monitor Mus Names Neuroendocrine Tumors Neurosecretory Systems New Agents Non-Small-Cell Lung Carcinoma Normal Statistical Distribution Octreotide Organ Patients Peptide Fragments Peptides Pharmaceutical Preparations Phase Photons Physicians Positron-Emission Tomography Principal Investigator Process Prodrugs Production Property Qualifying Radio Radioisotopes Radiometry Rattus Records Refractory Reporting Research Safety Shipping Ships Site Small Business Innovation Research Grant Solutions Somatostatin Somatostatin Receptor Source Specificity Sterility Symptoms Testing Therapeutic Therapeutic Agents Therapeutic Human Experimentation Thymoma Thyroid Diseases TimeLine Tissues Validation Work analytical method base clinical research site design dosimetry drug development efficacy testing financial incentive follow-up human subject in vivo innovation insight interest meetings meningioma metal chelator microbial alkaline proteinase inhibitor molecular imaging patient safety pre-clinical preclinical toxicity receptor research clinical testing scale up stability testing synthetic peptide tumor whole body imaging

项目摘要

DESCRIPTION (provided by applicant): A kit based PET agent: edotreotide Ga 68 for clinical imaging of somatostatin receptor expressing tissue. Synthetic peptides targeted to Somatostatin receptors (SSTR) were developed almost 30 years ago by Novartis to inhibit the effects of endogenous growth factors on malignant tissues. The radio-therapeutic version has been licensed to Molecular Insight (MIP) and the company is moving forward with phase 3 clinical testing of in somatostatin refractory patients. GMP manufacturing of the API peptide and therapeutic freeze dried kits have been performed by MIP. An approved diagnostic agent, to image SSTR expressing tumors, Indium-111 Octreoscan is already commercial available, although the photon emitting isotope produces low quality images and is not quantitative. Numerous academic centers outside the US have been performing PET imaging with edotreotide Ga-68 and two commercial gallium-68 generators have become available. Clinical studies have demonstrated PET imaging with edotreotide Ga 68 in thyroid disease, neuroendocrine tumors, gastrinomas, carcinoid, meningiomas, prostate cancer, thymoma, non- small cell lung carcinoma and as a potential in vivo monitor of therapeutic drug development and genomic medicine research. The goal of this proposal is to make sterile, GMP quality imaging formulation kits of edotreotide available for generation of the PET agent to image somatostatin receptor expressing tissue. Specifically, the GMP campaign for imaging edotreotide kits will be initiated and a physician sponsored safety assessment IND will be conducted for edotreotide Ga-68 (with our collaborators at Mass General Hospital). The Chemistry, manufacturing and controls for the final drug product solution along with a normal human image data base and human safety reports will be generated. Pre-clinical biological comparability studies and preclinical toxicity data on the API and precursor, will be combined with the human phase 1 data and made available to the SNM Clinical trial Network and be made available to widely dispersed clinical sites as amended INDs for research and efficacy testing. An innovative collaboration between NCI, FDA, CMS, industry and clinicians to accelerate and expand the availability of PET imaging biomarkers would have a significant impact on the fields of medicine research, therapeutic treatment monitoring and new drug development. PUBLIC HEALTH RELEVANCE: A kit based PET agent: edotreotide Ga 68 for clinical imaging of somatostatin receptor expressing tissue. The challenge for diagnostic drugs is their occasional use does not provide a financial incentive to develop new agents. Providing a consistent high quality agent for testing various potential indications at multiple clinical sites s paramount to obtaining innovative new products. We plan to make sterile high quality kits for production of edotreotide Ga 68 to facilitate community access to this investigational molecular imaging biomarker.

描述（由申请人提供）：基于试剂盒的PET试剂：edotreotide Ga 68，用于生长抑素受体表达组织的临床成像。大约 30 年前，诺华公司开发了针对生长抑素受体 (SSTR) 的合成肽，用于抑制内源性生长因子对恶性组织的影响。放射治疗版本已获得 Molecular Insight (MIP) 的许可，该公司正在推进生长抑素难治性患者的 3 期临床测试。 API 肽和治疗性冻干试剂盒的 GMP 生产已由 MIP 进行。 Indium-111 Octreoscan 是一种经批准的诊断剂，可对表达 SSTR 的肿瘤进行成像，现已上市销售，尽管光子发射同位素产生的图像质量较低且不是定量的。美国以外的许多学术中心一直在使用 edotreotide Ga-68 进行 PET 成像，并且已经推出了两台商用镓 68 发生器。临床研究已经证明，在甲状腺疾病、神经内分泌肿瘤、胃泌素瘤、类癌、脑膜瘤、前列腺癌、胸腺瘤、非小细胞肺癌中使用edotreotide Ga 68进行PET成像，并可作为治疗药物开发和基因组医学研究的潜在体内监测器。该提案的目标是制造无菌、GMP 质量的艾曲肽成像制剂试剂盒，用于生成 PET 试剂，以对表达生长抑素受体的组织进行成像。具体来说，将启动针对 edotreotide 成像试剂盒的 GMP 活动，并将对 edotreotide Ga-68 进行医生赞助的安全性评估 IND（与我们在麻省总医院的合作者一起）。将生成最终药品解决方案的化学、制造和控制以及正常的人体图像数据库和人体安全报告。 API 和前体的临床前生物可比性研究和临床前毒性数据将与人体 1 期数据相结合，提供给 SNM 临床试验网络，并作为修订后的 IND 提供给广泛分散的临床中心，用于研究和疗效测试。 NCI、FDA、CMS、行业和临床医生之间的创新合作将加速和扩大 PET 成像生物标志物的可用性，这将对医学研究、治疗监测和新药开发领域产生重大影响。公共健康相关性：基于试剂盒的 PET 试剂：edotreotide Ga 68，用于生长抑素受体表达组织的临床成像。诊断药物面临的挑战是它们的偶尔使用并不能提供开发新药物的经济激励。提供一致的高质量试剂以在多个临床地点测试各种潜在适应症对于获得创新新产品至关重要。我们计划制作用于生产 edotreotide Ga 68 的无菌高质量试剂盒，以促进社区获得这种研究性分子成像生物标志物。