Quantitative optical dosimetry of magnetic nanoparticle cancer treatments

磁性纳米颗粒癌症治疗的定量光学剂量测定

• 批准号: 8893022
• 负责人: Stephen Chad Kanick
• 金额: $ 16.76万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8893022
• 关键词: Address; Area; Breast; Breast Cancer Treatment; Cancer Biology; Cancer Center; Cancer Diagnostics; Clinical; Clinical Research; Clinical Trials; Clinical assessments; Concentration measurement; Data; Devices; Dextrans; Diagnosis; Dose; Educational workshop; Evaluation; Fiber Optics; Fluorescence; Funding; Goals; Grant; Head and Neck Cancer; Health; Heating; Human; Individual; Injection of therapeutic agent; Intravenous; Kinetics; Knowledge; Light; Magnetic nanoparticles; Malignant Neoplasms; Measurement; Measures; Mediating; Mentors; Metabolism; Methods; Monitor; Nanotechnology; Needles; Normal tissue morphology; Operative Surgical Procedures; Optics; Property; Radiation Oncology; Research; Research Personnel; Research Project Grants; Route; Sampling; Schedule; Selection for Treatments; Solid; Starch; Structure; Study of magnetics; Surface; System; Techniques; Technology; Temperature; Testing; Therapeutic; Time; Tissues; Training; Training Programs; Translations; Treatment Failure; Treatment outcome; United States National Institutes of Health; Validation; Variant; Vascular Patency; Veterinary Medicine; absorption; base; bioimaging; cancer imaging; cancer therapy; clinical investigation; clinical practice; college; cytotoxicity; design; dosimetry; experience; imaging system; in vivo; individualized medicine; innovation; interest; interstitial; iron oxide; knowledge base; lectures; magnetic field; magnetic therapy; medical schools; member; minimally invasive; multidisciplinary; nanoparticle; neoplastic cell; novel; optical imaging; photonics; pre-clinical; prognostic value; programs; response; targeted treatment; therapy design; translational medicine; tumor; tumor growth; uptake

DESCRIPTION (provided by applicant): The goal of this proposal is to allow the PI to become a leading member of a multidisciplinary biomedical team that develops photonics-based systems to diagnose and treat cancer, with a focus on clinical translation of emerging nanoparticle technologies. This proposal outlines a mentored-training program, which places the candidate within a cluster of NIH funded researchers, including an NIH Center of Cancer Nanotechnology Excellence at Dartmouth (DCCNE). The plan involves 4 complementary areas of focus: 1) building a firmer base of cancer biology knowledge; 2) developing superior theoretical and experimental expertise in standard biomedical imaging systems; 3) experience leading a pre-clinical investigating of an experimental nanoparticle anti-cancer treatment; and 4) experience in translation of a developed approach/device into an ongoing clinical trial. To achieve these goals the candidate will use the funding to dedicate time to participate in graduate cancer, imaging, and translational medicine courses at the College and Medical School, and to attend cancer workshops, training seminars and grand rounds lectures. This knowledge base will be applied within an ongoing program project conducted by DCCNE, which is carrying out human trials in magnetic-nanoparticle (mNP)-mediated alternating magnetic field (AMF) therapy as a targeted treatment for solid malignant tumors. The DCCNE teams lack a practical method to quantitatively determine the distribution of mNPs within a selected tissue of interest following administration, a critical limitation given the large variance in structure and vascularity between tumor types. The research project component of this proposal will utilize a novel optical system design to probe absorption and fluorescence to quantitatively estimate mNP distribution in vivo, returning mNP concentrations independent of distortions from background optical properties. The 4 research aims of this project investigate the concept that mNP-AMF therapy requires accurate dosimetry of mNP uptake in order to quantitatively interpret, and optimally reduce, the individual variation expected between subjects. Aim (1) is to design a novel optical device that will be validated for quantitative optical measurements of mNP in tissues in vivo. Aim (2) is to characterize the mNP uptake and distribution of mNPs in both tumor and surrounding normal tissues in vivo. Aim (3) will use quantitative dosimetry to monitor and optimize therapeutic dose delivered during preclinical mNP-AMF treatments. The prognostic value of mNP uptake measurements will be assessed by comparison with tumor growth delay. These data will be used to test the hypothesis that tumor- specific mNP-AMF dosimetry can optimize the delivered dose by reducing variability in treatment outcome. Aim (4) is to integrate these optical techniques to obtain observational measurements into an ongoing pilot clinical study of mNP-AMF for treatment of breast cancer. Data acquired in this trial will be retrospectively analyzed to determine correlation between tumor response and measured mNP concentrations at the time of treatment. This proposal includes a multi-disciplinary group of mentors that possess expertise in cancer biology, surgery, radiation oncology, veterinary medicine, biomedical optics and imaging, clinical practice, and clinical translation and have ample expertise in NIH funding.

描述（由申请人提供）：本提案的目标是让PI成为多学科生物医学团队的领导成员，该团队开发基于光子学的系统来诊断和治疗癌症，重点是新兴纳米颗粒技术的临床转化。该提案概述了一个指导培训计划，该计划将候选人置于NIH资助的研究人员集群中，包括位于达特茅斯的NIH癌症纳米技术卓越中心（DCCNE）。该计划涉及4个互补的重点领域：1）建立癌症生物学知识的坚实基础; 2）在标准生物医学成像系统中发展上级理论和实验专业知识; 3）领导实验性纳米颗粒抗癌治疗的临床前研究的经验;以及4）将开发的方法/设备转化为正在进行的临床试验的经验。为了实现这些目标，候选人将利用资金投入时间参加学院和医学院的研究生癌症，成像和转化医学课程，并参加癌症研讨会，培训研讨会和大型巡回讲座。该知识库将应用于DCCNE正在进行的一个项目中，该项目正在进行磁性纳米颗粒（mNP）介导的交变磁场（AMF）疗法作为实体恶性肿瘤靶向治疗的人体试验。DCCNE团队缺乏一种实用的方法来定量确定mNP在选定的感兴趣组织中的分布， 给药，这是一个关键的限制，因为在结构和血管分布之间存在很大的差异。 肿瘤类型该提案的研究项目组成部分将利用一种新型的光学系统设计来探测吸收和荧光，以定量估计体内mNP分布，返回mNP浓度独立于背景光学特性的失真。本项目的4个研究目标调查了mNP-AMF治疗需要准确的mNP摄取剂量测定的概念，以便定量解释并最佳减少受试者之间预期的个体差异。目的（1）是设计一种新的光学装置，将被验证用于定量光学测量体内组织中的mNP。目的（2）是表征体内肿瘤和周围正常组织中mNP的摄取和分布。目的（3）将使用定量剂量测定法来监测和优化临床前mNP-AMF治疗期间递送的治疗剂量。将通过与肿瘤生长延迟比较来评估mNP摄取测量的预后价值。这些数据将用于检验肿瘤特异性mNP-AMF剂量测定法可以通过减少治疗结果的变异性来优化递送剂量的假设。目的（4）是将这些光学技术整合到正在进行的mNP-AMF治疗乳腺癌的初步临床研究中，以获得观察性测量。将对本试验中获得的数据进行回顾性分析， 确定肿瘤反应与治疗时测量的mNP浓度之间的相关性。该提案包括一个多学科的导师小组，他们拥有癌症生物学，外科手术，放射肿瘤学，兽医学，生物医学光学和成像，临床实践和临床翻译方面的专业知识，并在NIH资助方面拥有丰富的专业知识。

项目成果

Wide-field quantitative imaging of tissue microstructure using sub-diffuse spatial frequency domain imaging.

• DOI: 10.1364/optica.3.000613
• 发表时间: 2016-06-20
• 期刊: Optica
• 影响因子: 10.4
• 作者: McClatchy DM 3rd;Rizzo EJ;Wells WA;Cheney PP;Hwang JC;Paulsen KD;Pogue BW;Kanick SC
• 通讯作者: Kanick SC