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

描述（由申请人提供）：一种基于PET试剂的试剂盒：edotreotide Ga 68，用于生长抑素受体表达组织的临床成像。针对生长抑素受体（SSTR）的合成肽是诺华公司近30年前开发的，用于抑制内源性生长因子对恶性组织的影响。放射治疗版本已授权给Molecular Insight (MIP)，该公司正在推进生长抑素难治性患者的3期临床试验。原料药肽和治疗性冻干试剂盒的GMP生产已由MIP进行。铟-111 Octreoscan是一种被批准的诊断试剂，用于对表达SSTR的肿瘤进行成像，虽然光子发射同位素产生的图像质量较低，而且不能定量，但它已经商业化。美国以外的许多学术中心已经在使用edotreotide Ga-68进行PET成像，两个商用镓-68发生器已经可用。临床研究表明，edotreotide Ga 68在甲状腺疾病、神经内分泌肿瘤、胃内膜瘤、类癌、脑膜瘤、前列腺癌、胸腺瘤、非小细胞肺癌等疾病中的PET显像具有潜在的治疗药物开发和基因组医学研究的体内监测价值。本提案的目标是制造无菌的、GMP质量的edotreotide成像配方试剂盒，用于生成PET剂，对表达生长抑素受体的组织进行成像。具体而言，将启动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）。将生成最终药品溶液的化学、制造和控制，以及正常的人体图像数据库和人体安全报告。原料药和前体的临床前生物学可比性研究和临床前毒性数据将与人类1期数据相结合，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站点，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。

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.