Molecular Imaging of CD46

项目摘要 CD 46在多种癌症中高度表达，包括腺癌和腺癌。 转移性去势抵抗性前列腺癌（mCRPC）的神经内分泌类型。其表达 在正常组织中，除妊娠期间的胎盘滋养层外， 前列腺上皮细胞程度较轻。抗CD 46抗体-药物缀合物（ADC）最初 Liu实验室开发的药物目前正在美国五个mCRPC中心进行I期试验。加州大学旧金山分校是领先的 试验中心（由重要贡献者Rahul Aggarwal博士领导）和第一名患者已接受给药。 这种类型的治疗的一个重要挑战是适当选择CD 46阳性细胞。 对治疗有反应的病人一种测定CD 46阳性的方法是通过 组织取样。然而，活检并不能反映所有病变中的靶表达， 具有特定肿瘤转移病灶的特征。相比之下，非侵入性分子成像 使用抗CD 46放射性示踪剂将允许抗原表达的全身评估， 从而鉴定可能对这种新疗法有反应的患者。CD 46具有 最近被发现作为晚期前列腺癌的新靶点;因此， 关于CD 46的全身表达的基本信息的缺口，其与 表达与肿瘤生长和转移形成的关系。此外，最近发现， 靶向，CD 46分子成像有助于了解特定的分子改变 与CD 46表达有关。 该提案的目标是开发一个用于分子成像的平台， CD46。我们将开发一组能够对CD 46进行非侵入性成像的放射性药物。 该平台不仅有可能识别可能对治疗产生应答的mCRPC患者， CD 46 ADC和其他新兴疗法，但也探索其他肿瘤中的CD 46表达 特别关注那些目前预后和生存率非常差的类型。的 本研究所收集到的信息对新疗法的开发可能起到重要作用。

PROJECT SUMMARY CD46 is highly expressed in multiple cancers, including both adenocarcinoma and neuroendocrine types of metastatic castration resistant prostate cancer (mCRPC). Its expression on normal tissue is generally low except for placental trophoblasts during pregnancy and to a lesser degree the prostate epithelium. An anti-CD46 antibody-drug conjugate (ADC) originally developed in the Liu lab is now in phase I trials at five US centers for mCRPC. UCSF is the leading test site (led by significant contributor Dr. Rahul Aggarwal) and the first patient has been dosed. An important challenge for this type of therapy is the appropriate selection of CD46-positive patients who will likely respond to therapy. One method to assay CD46 positivity would be through tissue sampling. However, biopsies do not reflect target expression in all lesions but rather the characteristic of a specific tumor metastatic lesion. In contrast, non-invasive molecular imaging using anti-CD46 radiotracers will allow for whole body assessment of antigen expression and consequently identification of patients who are likely to respond to this novel therapy. CD46 has been very recently discovered as a novel target of advanced prostate cancer; therefore, there is a gap in fundamental information about whole body expression of CD46, relationship between its expression and tumor growth and metastasis formation. Moreover, as a recently discovered target, molecular imaging of CD46 could contribute to understand specific molecular alterations related to CD46 expression. The goal of this proposal is the technical development of a platform for molecular imaging of CD46. We will develop a panel of radiopharmaceuticals capable of non-invasively imaging CD46. This platform will not only has the potential to identify mCRPC patients that will likely respond to CD46 ADC and other emerging therapies but also to explore CD46 expression in other tumor types with special attention to those that currently has very poor prognosis and survival. The information gather in this project may play an important role in the development on new therapies.