Light Scatter In Vivo Flow Cytometry to Monitor Cancer

描述（由申请人提供）：该R21/R33组合提案的主要目标是开发和评价基于光散射的体内流式细胞术（LSIVFC），这是一种用于定量监测不同循环血细胞群（包括癌细胞和白色血细胞）的新方法。如果成功，LSIVFC将作为一种非侵入性方法在癌症患者人群的临床管理中具有重要应用：a）检测循环癌细胞，其可特别用于检测癌症治疗后的微小残留疾病，B）监测化学预防的效果，光动力治疗和骨髓移植以优化治疗c）提高我们对循环癌细胞与转移或复发潜力之间关系的理解。为了实现这一目标，该项目涉及在生物医学仪器和光谱学，肿瘤生物学，组织工程，再生医学和血液学方面具有专业知识的科学家和临床医生之间的密切合作。在R21阶段，我们将专注于体外研究，旨在建立波长和角度相关的光散射区域，优化不同的感兴趣的血细胞群体的检测，如癌细胞和白色血细胞（WBC）（目标1）。将使用血液微循环体外模型（Aim 2）评价该方法的能力。利用从这些体外研究中获得的信息，我们将对少量动物进行测量，以说明LSIVFC研究用于监测循环癌症和WBC的可行性（目标3）。在R33阶段，我们将开发和优化该技术用于体内数据采集和分析（目标1和5），我们将说明LSIVFC在疾病进展和治疗反应（目标2）、骨髓移植（目标3）和WBC活化（目标4）中检测循环前列腺癌和白血病细胞的潜在临床和基础研究应用。这项建议对改善市民的健康，特别是对癌症病人的照顾，有很大的关系。开发一种用于监测循环白色血和癌细胞的非侵入性方法将提供一种用于检测癌症和密切监测个体患者对给定治疗的反应的非侵入性、无痛且可能更敏感的方法。

DESCRIPTION (provided by applicant): The main goal of this combined R21/R33 proposal is the development and evaluation of light-scattering based in vivo flow cytometry (LSIVFC), a novel method for the quantitative monitoring of different circulating blood cell populations, including cancer cells and white blood cells. If successful, LSIVFC will have significant applications in the clinical management of cancer patient populations, as a non-invasive method for: a) detecting circulating cancer cells, which may be particularly useful in the detection of minimal residual disease after cancer treatment, b) monitoring the effects of chemoprevention, photodynamic treatment and bone marrow transplantation to optimize treatment c) improving our understanding of the relationship between circulating cancer cells and the metastatic or relapse potential. To achieve this, the project involves close collaborations between scientists and clinicians with expertise in biomedical instrumentation and spectroscopy, tumor biology, tissue engineering, regenerative medicine and hematology. In the R21 phase, we will concentrate on in vitro studies, aimed to establish the wavelength-and angle-dependent light scattering regions that optimize detection of distinct blood cell populations of interest, such as cancer cells and white blood cells (WBCs) (Aim 1). The capabilities of this method will be evaluated using in vitro models of blood microcirculation (Aim2). Using the information acquired from these in vitro studies, we will perform measurements with a small number of animals to illustrate the feasibility of LSIVFC studies for monitoring circulating cancer and WBCs (Aim 3). In the R33 phase, we will develop and optimize this technology for in vivo data acquisition and analysis (Aims 1 and 5) and we will illustrate the potential clinical and basic research applications of LSIVFC in the context of detection of circulating prostate cancer and leukemic cells during disease progression and in response to treatment (Aim 2), bone marrow transplantation (Aim 3) and WBC activation (Aim 4). This proposal is highly relevant to the improvement of public health and to the care provided to cancer patients in particular. The development of a non-invasive method for monitoring circulating white blood and cancer cells would provide a non-invasive, painless and potentially more sensitive method for detecting cancer and monitoring closely the response of individual patients to a given treatment.