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

• 批准号: 8475431
• 负责人: JAMES F KRONAUGE
• 金额: $ 43.74万
• 依托单位: INVICRO, LLC
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-17 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8475431
• 关键词: kit; based; PET; agent; edotreotide

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.

描述（由申请人提供）：基于试剂盒的PET试剂：用于生长抑素受体表达组织的临床成像的依多曲肽Ga 68。靶向生长抑素受体（SSTR）的合成肽是近30年前由诺华公司开发的，用于抑制内源性生长因子对恶性组织的影响。放射治疗版本已被许可给分子洞察（MIP），该公司正在推进生长抑素难治性患者的3期临床试验。API肽和治疗性冻干试剂盒的GMP生产已由MIP进行。一种被批准的诊断剂，用于对表达SSTR的肿瘤进行成像，铟-111 Octreoscan已经是商业可用的，尽管光子发射同位素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已经使用依多曲肽Ga-68进行PET成像，并且已经有两种商业镓-68发生器可用。临床研究已经证明了在甲状腺疾病、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依多曲肽Ga 68的PET成像，并且作为治疗药物开发和基因组医学研究的潜在体内监测器。本提案的目的是制造无菌的、GMP质量的依多曲肽成像制剂试剂盒，用于生成PET试剂以使生长抑素受体表达组织成像。具体而言，将启动成像依多曲肽试剂盒的GMP活动，并将对依多曲肽Ga-68进行医生申办的安全性评估IND（与我们在麻省总医院的合作者一起）。将生成最终制剂溶液的化学、生产和控制沿着正常人体图像数据库和人体安全性报告。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I期数据相结合，并提供给SNM临床试验网络，并作为修订的IND提供给广泛分布的临床研究中心，用于研究和疗效试验。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，治疗监测和新药开发领域产生重大影响。