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Project 1: Development of Mechanical Interventions to Enhance Drug Delivery to Bone Tumors

项目 1：开发机械干预措施以增强骨肿瘤的药物输送

基本信息

批准号：
10021560
负责人：
SUSANNAH P. FRITTON
金额：
$ 9.96万
依托单位：
CITY COLLEGE OF NEW YORK
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-26 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10021560
关键词：
Antineoplastic Agents Area Biomedical Engineering Bone Diseases Bone neoplasms Cancerous Cities Clinic Clinical Clinical Data Clinical Protocols Clinical Research Clinical Treatment Collaborations Community Outreach Contralateral Control Groups Core Facility Data Deterioration Development Devices Disease Drug Delivery Systems Education and Outreach Exercise Fluorine Future Genes Goals Head Human Injections Institutional Review Boards Intervention Intravenous Isotopes Lower Extremity Malignant neoplasm of prostate Mammary Neoplasms Mechanics Medical Oncologist Memorial Sloan-Kettering Cancer Center Metastatic Neoplasm to the Bone Modality Modeling Morbidity - disease rate Neoplasm Metastasis New York Orthopedics PET/CT scan Paclitaxel Patients Pharmaceutical Preparations Phase I Clinical Trials Physiological Pilot Projects Positron-Emission Tomography Principal Investigator Protocols documentation Quality of life Radio Radiolabeled Rattus Research Personnel Research Training Risk Skeleton Spinal Students Surgeon Testing Therapeutic Therapeutic Agents Therapeutic Effect Translating Tumor Burden Universities Vertebral column Walking Weight-Bearing state Work animal imaging anticancer research base bone bone imaging cancer cell chemotherapeutic agent clinical application clinically relevant clinically translatable college design dosage drug distribution experimental study improved malignant breast neoplasm mechanical load microPET novel strategies pre-clinical preclinical study side effect skeletal tibia treadmill tumor uptake vibration

项目摘要

The objective of this study is to develop and validate clinically translatable mechanical interventions that can be used to enhance drug delivery to cancerous bone tumors. In preliminary work, the City College of New York (CCNY) and Memorial Sloan Kettering Cancer Center (MSKCC) investigative team has demonstrated that delivery of an intravenous drug can be significantly enhanced in mechanically loaded tumor-bearing rat tibiae. Based on the promising preliminary results, this study will collect important pre-clinical data that will test two different mechanical interventions in a rat model and then translate the results to develop a clinical protocol to enhance drug delivery to bone tumors. Two different approaches of applying mechanical intervention will be used to enhance tumor drug delivery in a rat model of metastatic bone cancer to assess their potential applicability to human patients. Specific Aim 1 will simulate how exercise would be used in the clinic to enhance drug delivery to bone tumors. Specific Aim 2 will utilize very low-magnitude mechanical vibration that could also be delivered easily in a clinical setting. Specific Aim 3 will build upon the findings from the pre- clinical rat studies to design a clinical IRB protocol that would target patients most likely to benefit from mechanical intervention during cancer drug administration. The long-term goal of this work is to establish a clinical treatment that uses load-bearing exercise or low-intensity vibration to enhance tumor delivery of therapeutic drugs. This low-risk and easy-to-implement approach may enhance a drug's uptake and therapeutic effect in the most clinically relevant skeletal areas while potentially decreasing systemic drug dosage and unwanted side effects.

本研究的目的是开发和验证临床上可翻译的机械干预，用于增强对癌性骨肿瘤的药物输送。在初步工作中，纽约城市学院（CCNY）和纪念斯隆凯特琳癌症中心（MSKCC）的调查小组已经证明，静脉内药物的递送在机械负载的荷瘤大鼠体内可显著增强。基于有希望的初步结果，这项研究将收集重要的临床前数据，在大鼠模型中进行不同的机械干预，然后将结果转化为临床方案，增强骨肿瘤的药物递送。将介绍两种不同的机械干预方法，用于增强转移性骨癌大鼠模型中的肿瘤药物递送，以评估其潜力适用于人类患者。具体目标1将模拟如何在临床中使用锻炼，增强骨肿瘤的药物递送。具体目标2将利用非常低幅度的机械振动，也可以在临床环境中容易地递送。具体目标3将建立在前- 临床大鼠研究，以设计临床IRB方案，针对最有可能受益于癌症药物给药期间的机械干预。这项工作的长期目标是建立一个使用承重运动或低强度振动来增强肿瘤输送的临床治疗治疗药物这种低风险和易于实施的方法可以提高药物的吸收，在最具临床相关性的骨骼区域具有治疗作用，同时可能减少全身药物剂量和不良副作用。