Developing a plectin-1 targeted imaging agent for the detection of pancreatic can

描述（由申请人提供）：胰腺导管腺癌（PDAC）是一个棘手的临床问题，通常在诊断时出现转移，并对现有疗法表现出严重的耐药性。目前，标准诊断过程包括CT或MRI扫描，其不具有用于准确诊断和确定可切除性状态的最佳灵敏度和特异性。本项目的长期目标是开发一种能够灵敏、准确地检测胰腺癌的显像剂。为此，我们正在开发一种针对新发现的胰腺癌细胞表面生物标志物plectin-1的靶向成像剂。Plectin-1在胰腺癌中特异性表达，而在良性炎症中不表达。它在癌发生过程中上调，并在晚期转移前PanIN III病变中高水平表达。此外，SPECT/CT plectin-1靶向成像剂已在许多严格的小鼠模型中开发和验证。将进行实验以优化成像剂的分子构型和成像模式。结果将导致一个领先的成像产品，将提前到第二阶段的商业产品开发和临床研究。 公共卫生相关性：该项目的总体目标是开发用于检测胰腺癌的新的成像方法，确定癌症可切除性状态并监测对化疗的反应。替代用途包括对胰腺癌高危人群进行早期诊断筛查。我们将通过化学合成成像剂并在胰腺癌小鼠模型中进行测试来实现这一目标。我们还将测试PET或SPECT成像是否具有胰腺癌成像的最佳特征。

DESCRIPTION (provided by applicant): Pancreatic ductal adenocarcinoma (PDAC) is an intractable clinical problem, typically presenting with metastasis at the time of diagnosis and exhibiting profound resistance to existing therapies. Currently, the standard diagnostic course includes CT or MRI scans which do not have optimal sensitivity and specificity for accurately diagnosing and determining resectability status. The long-term objectives of this project are to develop an imaging agent that can sensitively and accurately detect pancreatic cancer. To that end, we are developing a targeted imaging agent to the newly identified pancreatic cancer cell surface biomarker plectin-1. Plectin-1 is specifically expressed in pancreatic cancer and not in benign inflamed conditions. It is upregulated during carcinogenesis and expressed at high levels in the advanced premetastatic PanIN III lesions. Moreover, a SPECT/CT plectin-1 targeted imaging agent has been developed and validated in numerous stringent mouse models. Experiments will be performed to optimize the imaging agent's molecular configuration and imaging modality. Outcomes will lead to a lead imaging product that will be advanced to phase II for commercial product development and clinical study. PUBLIC HEALTH RELEVANCE: The overall goal of this project is to develop new imaging approaches for the detection of pancreatic cancer, determine cancer resectability status and monitor response to chemotherapy. Alternative uses include early diagnostic screening in individuals with high-risk for the development of pancreatic cancer. We will do this by chemically synthesizing imaging agents and testing them in mouse models of pancreatic cancer. We will also test whether PET or SPECT imaging has the best characteristics for imaging pancreatic cancer.