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）：基于套件的宠物剂：用于生长抑素受体表达组织的临床成像的edotreotide GA 68。大约30年前，诺华开发了针对生长抑素受体（SSTR）的合成肽，以抑制内源性生长因子对恶性组织的影响。无线电治疗版本已获得分子见解（MIP）的许可，该公司正在向三阶段的生长抑素难治性患者进行3阶段临床测试。 API肽的GMP制造和治疗冻结套件已通过MIP进行。鉴于SSTR表达肿瘤的批准的诊断剂，inspreoscan已经可以商业化，尽管光子发射同位素会产生低质量的图像，并且不是定量的。美国以外的许多学术中心都使用Edotreotide GA-68进行宠物成像，并且已经有两个商用的镀与68发电机可用。临床研究表明，在甲状腺疾病，神经内分泌肿瘤，胃瘤，类癌，脑膜炎瘤，前列腺癌，胸腺瘤，非小细胞肺癌以及作为治疗药物发育和种植体药物研究的潜在潜力的甲状腺疾病，神经内分泌瘤，癌瘤，前列腺癌，脑膜癌，胸膜癌，非小细胞肺癌，脑膜炎，脑膜癌，脑膜癌，胸膜癌，非小细胞癌。该提案的目的是制造无菌的GMP质量成像配方试剂盒可用于生成宠物剂，以形象表达生长抑素受体。具体而言，将启动用于成像edotreotide套件的GMP运动，并将针对Edotreotide GA-68（我们在Mass General Hospital的合作者）进行医师赞助的安全评估IND。将生成最终药物解决方案的化学，制造和控制以及正常的人类图像数据库和人类安全报告。临床前的生物学可比性研究和API和前体上的临床前毒性数据将与人类1期数据结合使用，并可用于SNM临床试验网络，并可以通过对研究和效率测试进行修订的INDS进行广泛分散的临床部位。 NCI，FDA，CMS，行业和临床医生之间的创新合作，以加速和扩大PET成像生物标志物的可用性将对医学研究，治疗治疗监测和新药物开发的领域产生重大影响。公共卫生相关性：基于试剂盒的宠物剂：用于生长抑素受体表达组织的临床成像的edotreotide GA 68。诊断药物面临的挑战在于它们偶尔的使用并不能提供发展新代理商的经济动力。为在多个临床部位的各种潜在指示测试获得创新的新产品的最重要的高质量代理提供了一致的高质量代理。我们计划制作无菌的高质量套件，用于生产edotreotide GA 68，以促进社区进入该研究性分子成像生物标志物。