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

描述(由申请人提供)：一种基于试剂盒的PET试剂：依多曲肽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肿瘤组织的影响。放射治疗版本已经授权给分子洞察公司(MIP)，该公司正在推进生长抑素难治性患者的第三阶段临床测试。MIP已经完成了原料药多肽和治疗性冷冻干燥试剂盒的GMP制造。作为一种被批准的诊断试剂，用于对表达肿瘤的SSTR进行成像，Indium-111 Octreoscan已经商业化，尽管这种发射光子的同位素产生的图像质量较低，而且不是定量的。美国以外的许多学术中心一直在使用依多曲肽Ga-68进行PET成像，两台商用镓-68发生器已经问世。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，使用依多曲肽GA 68进行PET成像是潜在的治疗药物开发和基因组医学研究的体内监测。这项建议的目标是使无菌、GMP质量的依多曲肽成像配方试剂盒可用于生成PET试剂，以成像生长抑素受体表达的组织。具体地说，将启动用于成像依多曲肽试剂盒的GMP活动，并将(与我们在马萨诸塞州综合医院的合作者)对依多曲肽GA-68进行医生赞助的安全性评估IND。将生成最终药物产品解决方案的化学、制造和控制，以及正常的人体图像数据库和人体安全报告。关于原料药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类第一阶段数据结合起来，提供给SNM临床试验网络，并作为修订的INDS提供给广泛分布的临床地点进行研究和疗效测试。NCI、FDA、CMS、业界和临床医生之间的创新合作，以加速和扩大PET成像生物标记物的可获得性，将对药物研究、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.