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Simultaneous Imaging of Tumor and Host Cells in the Microenvironment

微环境中肿瘤和宿主细胞的同步成像

基本信息

批准号：
10549299
负责人：
Megan Suzanne Michie
金额：
$ 3.36万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-01-01 至 2025-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10549299
关键词：
Adverse event Affect Affinity Aftercare Annexins Antibodies Atlas of Cancer Mortality in the United States Binding Bispecific Antibodies Breast Cancer Cell Breast Cancer Detection Breast Cancer Patient Breast Cancer Treatment Breast Cancer gene Breast Cancer therapy Cancer Biology Cancer Detection Cancer Etiology Cancerous Cause of Death Cells Cessation of life Circulation Clinical Detection Diagnosis Disease Disease Outcome Drug Kinetics Dyes ERBB2 gene Equilibrium Exhibits Fibroblasts Fluorescence Foundations Goals Histologic Image Image Enhancement Immune Immunotherapeutic agent Intervention Lesion Ligands Localized Disease Malignant Neoplasms Maps Measures Metastatic breast cancer Methods Microscopic Molecular Molecular Probes Molecular Target Monitor Mus Near-infrared optical imaging Neoplasm Metastasis Optics Outcome Patient-Focused Outcomes Patients Penetration Peptides Pharmaceutical Preparations Phosphorylation Population Prediction of Response to Therapy Process Prognosis Property Quality of life Recurrence Recurrent disease Recurrent tumor Regional Disease Reporting Research Residual Neoplasm Residual state Signal Transduction Specificity Stromal Cells Survival Rate Testing Therapeutic Time Tissues Transgenic Organisms Treatment outcome Tumor Biology Tumor Tissue Tumor Volume Woman Work cancer biomarkers cancer cell cancer imaging cancer therapy cell type chemotherapy design detection method detection sensitivity effective therapy fibroblast-activating factor fluorescence lifetime imaging fluorophore imaging agent imaging modality imaging platform imaging probe improved in vivo in vivo fluorescence malignant breast neoplasm microscopic imaging molecular imaging mortality mouse model neoplastic cell novel optical imaging optimal treatments overtreatment personalized medicine pre-clinical prognostic prognostic indicator side effect small molecule standard of care targeted agent targeted biomarker targeted imaging targeted treatment trait treatment planning treatment response triple-negative invasive breast carcinoma tumor tumor growth tumor microenvironment

项目摘要

Proposal Summary/Abstract While there have been significant advances in the detection and treatment of breast cancer, mortality due to metastatic disease recurrence remains unacceptably high and a leading cause of death. Furthermore, chemotherapies with intolerable side effects remain the standard of care for metastatic breast cancer patients, which is highly detrimental to quality of life. Advances in molecular targeting cancer imaging offer a window into underlying tumor biology and support the use of individualized targeted therapies that can spare patients over- treatment with harsh chemotherapies. However, most molecular imaging probes typically target either cancer cells or, more recently, a single cell type in the tumor microenvironment. These approaches are inherently limited in the information they can provide. Optimal treatment planning relies on a complete picture of disease state, including microscopic regions of residual disease and understanding the potential for recurrence based on a lesion’s specific molecular traits. As such, the goal of this proposal is to provide the foundation for a clinically useful means to image and understand disease status before, during, and after treatment of primary breast cancer and metastatic disease. We postulate that molecular imaging of both the microenvironment and cancer cells simultaneously will provide more complete detection of diseased regions and an understanding of dynamic changes in tumor microenvironment that are needed to support personalized therapy. We propose: (Aim1) A bispecific strategy targeting both breast cancer cells and cancer-associated fibroblasts in the tumor microenvironment to enhance tumor detection. (Aim 2) Differentially targeting cancer cells and cancer-associated fibroblasts with near-infrared molecular probes with similar spectral properties but different fluorescent lifetime values to extract tumor-stroma ratio noninvasively, which is a prognostic indicator in breast cancer. This non-invasive method of determining the relative abundance of malignant cells and cancer- associated fibroblasts will be compared with the traditional histologic determination of tumor-stroma ratio. At the completion of this study, we expect to have established a signal amplification method to detect small cancerous lesions and a non-invasive approach to map cancer-stromal ratio to understand how the dynamic changes in the tumor microenvironment affect cancer biology.

建议总结/文摘