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Early phase clinical trial for imaging tumor acidosis in breast cancer patients using acidoCEST MRI

使用 AcidoCEST MRI 对乳腺癌患者肿瘤酸中毒进行成像的早期临床试验

基本信息

批准号：
8948796
负责人：
Mark David Pagel
金额：
$ 34.99万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-06-19 至 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8948796
关键词：
Acidosis Address Aerobic Biological Markers Breast Cancer Patient Chemicals Clinic Clinical Clinical Research Clinical Trials Contrast Media Cyclophosphamide Diagnosis Dose Doxorubicin ERBB2 gene Engineering Ensure Estrogen Receptors Evaluation Glycolysis Histopathologic Grade Hypoxia Image In complete remission Institutional Review Boards Lactic acid Lymphoma MRI Scans Magnetic Resonance Imaging Malignant Neoplasms Maps Measurement Measures Metabolism Methods Modeling Monitor Neoadjuvant Therapy Normal tissue morphology Outcome Paclitaxel Patients Pharmaceutical Preparations Phase Phenotype Protocols documentation Reporting Research Personnel Resected SDZ RAD Testing Therapeutic Tissues Translating Translations Tumor Subtype Warburg Effect arm base cancer imaging carbonate dehydratase chemotherapy extracellular imaging modality improved in vivo innovation lymph nodes mTOR Inhibitor malignant breast neoplasm metaiodobenzylguanidine mouse model non-invasive imaging pre-clinical preclinical study prospective public health relevance receptor expression response standard care tool tumor tumor growth tumor metabolism tumor microenvironment tumor xenograft volunteer

项目摘要

DESCRIPTION (provided by applicant): We have developed a non-invasive imaging method that can quantitatively measure the extracellular pH (pHe) in tumors. Our MRI method uses Chemical Exchange Saturation Transfer (CEST) MRI to assess tumor acidosis, termed "acidoCEST MRI". We have recently translated acidoCEST MRI to a clinical 3T MRI scanner, we have tested volunteers with our protocol, we have an approved IRB protocol for our first clinical trial, and we have assembled an exceptionally strong team of investigators to perform our clinical studies. Therefore, all steps are in place to start our clinical trials. For Specific im 1, we propose to correlate tumor pHe in breast cancer patients with tumor subtype and ex vivo correlates of acidosis, hypoxia, and glycolysis. Our rationale is based on our extensive results from our pre-clinical studies that have shown how more aggressive tumor models have a higher tumor acidosis. We have also shown that tumor pHe is correlated with high expression of carbonic anhydrase IX, which is an established biomarker of tumor hypoxia. We will perform acidoCEST MRI scans with breast cancer patients, and obtain ex vivo correlates from resected tissues during their standard care. For Specific Aim 2, we propose to use acidoCEST MRI to monitor the early response to neoadjuvant chemotherapy in breast cancer patients. Our rationale is based on our pre-clinical imaging results that have shown how Everolimus (an mTOR inhibitor) raises tumor pHe in a lymphoma model within 1 day of initiating therapy, and then returns to an acidic state after 7 days of daily treatment, which foreshadowed the temporary tumor growth delay of this drug treatment. We will perform acidoCEST MRI scans before and 4 weeks after initiating neoadjuvant chemotherapy with dose dense doxorubicin-cyclophosphamide followed by paclitaxel. We will correlate initial tumor pHe and the change in tumor pHe with clinical outcome. Based on these results, our DELIVERABLE is an innovative, noninvasive imaging method that can generate parametric maps of tumor pHe, which can be used to improve diagnosis and evaluate early response to chemotherapy for breast cancer patients.