ROLE OF CYPA AS A MOLECULAR IMAGING OR THERAPEUTIC TARGET

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。亲环素A(CypA)在癌症中的作用尚不清楚。利用CypA表达下调的肺癌细胞和内源性CypA水平的对照细胞，我们已经进行了体外实验，并正在完成SCID小鼠皮下移植瘤的体内成瘤实验。这种蛋白质可能是分子成像和治疗的有用靶点。然而，考虑到CypA的未知角色，我们使用可用的资源来获得这些传统方法之外的尽可能多的数据是至关重要的。杜克大学活体显微镜中心的高质量PET成像设备将使我们能够以补充传统病理学的方式检查CypA在体内的作用。使用FDG-PET，我们可以比较基因敲除和对照动物的肿瘤大小、功能和代谢活性。我们还可以比较基因敲除动物和对照动物之间从原始异种皮下移植到远处的转移的存在和程度，这是一项特别适合于FDG-PET成像的实验。这一过程需要尾静脉注射FDG和PET扫描，相对来说是非侵入性的，应该不会对动物造成不必要的伤害

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The role of Cyclophilin A (CypA) is unknown in cancer. Using lung cancer cells which have CypA expression knocked down and control cells with endogenous CypA levels, we have performed in vitro assays and are completing in vivo assays of tumorigenesis with subcutaneous xenografts in SCID mice. This protein may be a useful target for molecular imaging and therapeutics. However, given the unknown role of CypA, it is crucial that we use available resources to get as much data as possible beyond these traditional methods. The high quality PET imaging equipment in the Duke Center for In Vivo Microscopy will allow us to examine the in vivo role of CypA in ways complementary to traditional pathology. Using FDG-PET, we may compare tumor size, function, and metabolic activity between knockdown and control animals. We may also compare the presence and degree of metastases from the primary subcutaneous xenograft to distant sites between knockdown and control animals, an experiment uniquely suited to FDG-PET imaging. The procedure entails a tail vein injection of FDG, and a PET scan, is relatively non-invasive, and should not cause undue harm to the animal