STTR Phase I: Novel Molecularly Targeted Tracer for Specific and Sensitive Imaging of Cancer

这个小企业技术转移一期项目采用了一种创新的肿瘤靶向方法，通过研究一种全新的肿瘤靶向平台，该平台利用骨髓衍生的循环肿瘤归巢细胞作为天然载体。通过筛选噬菌体展示肽库，我们已经确定了高亲和力的肽配体，以高特异性结合这些细胞。这些高亲和力、高特异性肽配体及其在肿瘤分子成像中的应用I’s blood supply是该一期工程的创新之处。放射性标记的多肽定向化合物将被合成，并具有传递分子有效载荷的潜力。特异性地对恶性脉管系统在小鼠肿瘤模型中进行表征。这项开发工作的结果将为一种新的靶向范式提供原理验证，在这种范式中，循环肿瘤定位细胞群可以用于高度变革性和创新性的技术开发，以造福癌症患者。该项目的广泛影响和这里开发的分子诊断示踪剂的商业化将对通过个性化方法进一步推进肿瘤护理具有重要意义：首先，基于循环细胞归巢监测的特异性和敏感成像将有利于肿瘤分期和再分期。第二，此外，这一发展努力的结果将提供迄今为止所缺乏的与治疗有关的更多可预测的信息。密切评估病人？通过监测循环肿瘤归巢细胞的存在或缺失来监测肿瘤对治疗的反应，将改善治疗结果，并指导个性化治疗的发展。第三，特别有前景的临床方向是选择性地提供抗血管生成和治疗性化合物作为抗癌策略。由于内源性细胞被用作天然的生物载体，我们创新的诊断示踪剂的商业化和临床应用的障碍比其他新兴技术要低得多。

This Small Business Technology Transfer Phase I project takes an innovative approach at tumor targeting by investigating an entirely novel tumor targeting platform that utilizes bone marrow derived, circulating tumor homing cells as natural vectors. Through screening of phage display peptide libraries we have identified high affinity peptide ligands that bind these cells with high specificity. These high affinity, high specificity peptide ligands and their applications for molecular imaging of tumor?s blood supply represent the innovation in this Phase I project. Radiolabeled peptide directed compounds will be synthersized and their potential to deliver molecular ?payloads? specifically to malignant vasculature in a mouse model of cancer will be characterized. The results from this development effort will provide proof-of-principle validation for a new targeting paradigm in which circulating tumor localizing cell populations can be exploited for highly transformative and innovative technology development for the benefit of cancer patients.The broader impact of this project and the commercialization of the molecular diagnostic tracer developed here will have important implications for furthering oncology care through personalized approaches: First, specific and sensitive imaging based on monitoring of homing of circulating cells to tumor tissue will be beneficial for tumor staging and re-staging. Second, in addition the outcomes of this development effort would provide more predictable information relevant to treatment that has been lacking so far. Close assessment of patient?s response to treatment by monitoring the presence or absence of circulating tumor homing cells would improve treatment outcomes and guide the development of personalized therapies. Third, especially promising clinical direction is to selectively deliver anti-angiogenic, and therapeutic compounds as anticancer strategies. Because endogenous cells are utilized as natural biologic vectors, the barriers to commercialization and clinical implementation of our innovative diagnostic tracer are much lower than for other emerging technologies.