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

开发用于检测胰腺癌的 plectin-1 靶向成像剂

基本信息

批准号：
8200534
负责人：
Greg Brian Fralish
金额：
$ 30万
依托单位：
ITI HEALTH, INC.
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-19 至 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8200534
关键词：
Abdomen Address Affinity Animal Model Animals Benign Binding Biological Markers Cell surface Characteristics Chemistry Clinical Clinical Research Comorbidity Detection Development Diagnosis Diagnostic Disease Drug Kinetics Early Diagnosis Emotional Stress Excision Exhibits Family Fine needle aspiration biopsy Goals Health High Pressure Liquid Chromatography Human Image In Vitro Individual Kidney Label Lead Lesion Life MRI Scans Magnetic Resonance Imaging Malignant Neoplasms Malignant neoplasm of pancreas Methods Molecular Conformation Monitor Mus Neoplasm Metastasis Newly Diagnosed Outcome Pancreas Pancreatic Ductal Adenocarcinoma Pancreatic Intraepithelial Neoplasia Patients Peptides Phase Positron-Emission Tomography Procedures Process Publishing Resectable Resistance Risk Factors Sampling Screening procedure Sensitivity and Specificity Serum Signs and Symptoms Staging Surface Surgeon Survival Rate Testing Therapeutic Human Experimentation Time Ultrasonography Work X-Ray Computed Tomography carcinogenesis chelation chemotherapy chronic pancreatitis clinically relevant cost dimer disorder control dosimetry high risk imaging modality improved in vivo manufacturing process molecular imaging monomer mouse model novel outcome forecast pancreatic cancer cells pancreatic neoplasm plectin product development research study response scale up single photon emission computed tomography tool tumor

项目摘要

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.

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，并且对现有疗法表现出深远的抵抗力。当前，标准诊断课程包括CT或MRI扫描，这些扫描没有最佳的敏感性和特异性，无法准确诊断和确定切除性状态。该项目的长期目标是开发一种成像剂，该成像剂可以敏感，准确地检测胰腺癌。为此，我们正在向新鉴定的胰腺癌细胞表面生物标记蛋白-1开发靶向成像剂。 PLECTIN-1在胰腺癌中特别表达，而不是在良性发炎的情况下表达。它在癌变期间被上调，并在晚期转移性panin III病变中以高水平表达。此外，在许多严格的小鼠模型中已经开发并验证了SPECT/CT PLECTIN-1靶向成像剂。将进行实验以优化成像剂的分子构型和成像方式。结果将导致铅成像产品，该产品将进入II阶段进行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成像方法，确定癌症可分离性状态并监测对化学疗法的反应。替代用途包括在胰腺癌发展的高风险患者中进行早期诊断筛查。我们将通过化学合成成像剂并在胰腺癌的小鼠模型中测试它们来做到这一点。我们还将测试PET或SPECT成像是否具有成像胰腺癌的最佳特征。