Molecular Imaging of Macrophage Infiltration in Solid Cancers

实体癌中巨噬细胞浸润的分子成像

• 批准号: 8645769
• 负责人: Joshua J. Rychak
• 金额: $ 22.5万
• 依托单位: TARGESON, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8645769
• 关键词: Accounting; Antibodies; Area; B-Lymphocytes; Binding; Biocompatible; Biological Assay; Biological Models; Biopsy; Blocking Antibodies; Cancer Patient; Cell Line; Cells; Chemistry; Clinical; Contrast Media; Coupled; Coupling; Data; Dendritic Cells; Development; Diagnostic; Drug Formulations; Enzyme-Linked Immunosorbent Assay; Evaluation; Feasibility Studies; Flow Cytometry; Growth; Healthcare; Image; Imagery; Immune; Immune response; Immunotherapy; In Vitro; Incubated; Infiltration; Injection of therapeutic agent; Ligand Binding; Ligands; MERTK gene; MHC Class II Genes; Malignant Neoplasms; Measurement; Mediating; Methods; Methylcholanthrene; Microbubbles; Monitor; Monoclonal Antibodies; Morbidity - disease rate; Mus; Nature; Patients; Phase; Phenotype; Population; Procedures; Publishing; Reagent; Recruitment Activity; Relative (related person); Research; Science; Signal Transduction; Site; Solid; Solid Neoplasm; Specificity; Staging; Staining method; Stains; Surface; Testing; Time; Transplantation; Ultrasonography; base; cancer therapy; cohort; density; efficacy testing; imaging probe; in vivo; insight; macrophage; molecular imaging; molecular marker; mortality; mouse model; non-invasive imaging; novel; outcome forecast; prognostic; public health relevance; response; sarcoma; subcutaneous; success; tumor; tumor growth; tumor progression; uptake

DESCRIPTION (provided by applicant): Treatment of cancer accounts for an increasing level of healthcare expense although patient morbidity and mortality remain relatively high. Current methods for assessing the extent of immune cell infiltration into cancers require invasive biopsy procedures that cannot be done on the same tumor over time, thus precluding longitudinal tracking of immune responses in patients. In the current project, we propose to develop a novel molecular imaging probe for visualization of macrophage infiltration into tumors. Specifically, we aim to develop a microbubble contrast agent targeted to a molecular marker of MHCII positive macrophages, thought to be indicative of a tumor rejection response. In this Phase I proposal, we will use an anti-mouse MHC class II antibody as a targeting ligand. Antibodies will be conjugated to the surface of an ultrasound molecular imaging agent using proven biocompatible coupling chemistry. We will validate ligand conjugation and microbubble stability, and assess the targeting efficacy of the resultant microbubble formulations in vitro and in a mouse model of tumor progression. We will use this imaging agent to quantitatively track the influx of macrophages in paired mouse models of tumor rejection and growth. Successful completion of these aims will result in a molecular imaging probe that may be used to accurately and rapidly identify the quality and quantity of tumor infiltrating macrophages, with applications as both a lie science research reagent and as a clinical diagnostic.

描述（由申请人提供）：尽管患者的发病率和死亡率仍然相对较高，但癌症的治疗占医疗保健费用的水平越来越高。目前评估免疫细胞浸润癌症程度的方法需要侵入性活组织检查，这种方法不能长期对同一肿瘤进行活检，因此无法对患者的免疫反应进行纵向跟踪。在目前的项目中，我们建议开发一种新的分子成像探针，用于巨噬细胞浸润肿瘤的可视化。具体来说，我们的目标是开发一种针对MHCII阳性巨噬细胞分子标记的微泡造影剂，该分子标记被认为是肿瘤排斥反应的指示物。在这个I期提案中，我们将使用抗小鼠MHC II类抗体作为靶向配体。抗体将被结合到超声分子显像剂的表面，使用经过验证的生物相容性偶联化学。我们将验证配体偶联性和微泡稳定性，并在体外和肿瘤进展小鼠模型中评估所得微泡制剂的靶向效果。我们将使用该显像剂定量跟踪配对小鼠肿瘤排斥和生长模型中巨噬细胞的流入。这些目标的成功完成将产生一种分子成像探针，可用于准确、快速地识别肿瘤浸润巨噬细胞的质量和数量，既可作为谎言科学研究试剂，也可作为临床诊断。