Quantitative optical dosimetry of magnetic nanoparticle cancer treatments

描述（由申请人提供）：该提案的目标是允许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)建立更坚实的癌症生物学知识基础；2)在标准生物医学成像系统方面发展卓越的理论和实验专业知识；3)有领导实验性纳米粒子抗癌治疗的临床前研究经验；4)将已开发的方法/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，候选人将利用这笔资金投入时间参加大学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粒子（mNP）介导的交变磁场（AMF）治疗作为实体恶性肿瘤的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mNPs在选定的感兴趣组织中的分布

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.