Light Scatter In Vivo Flow Cytometry to Monitor Cancer

描述(由申请人提供)：R21/R33联合提案的主要目标是开发和评估基于光散射的在体流式细胞术(LSIVFC)，这是一种用于定量监测不同循环血细胞群体的新方法，包括癌细胞和白细胞。如果成功，LSIVFC将在癌症患者的临床管理中有着重要的应用，作为一种非侵入性的方法：a)检测循环癌细胞，这可能在检测癌症治疗后最小的残留疾病方面特别有用；b)监测化学预防、光动力学治疗和骨髓移植的效果，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，该项目涉及拥有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，以优化对不同的感兴趣血细胞群体的检测，如癌细胞和白细胞(WBC)(目标1)。这种方法的能力将使用体外血液微循环模型(AIM2)进行评估。利用从这些体外研究中获得的信息，我们将用一小部分动物进行测量，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，我们将开发和优化这项用于体内数据采集和分析的技术(目标1和5)，我们将说明LSIVFC在检测疾病进展过程中循环前列腺癌和白血病细胞以及对治疗(目标2)、骨髓移植(目标3)和白细胞激活(目标4)的响应方面的潜在临床和基础研究应用。这项建议与改善公共健康，特别是向癌症患者提供的护理密切相关。非侵入性监测循环白血和癌细胞的方法的发展，将提供一种非侵入性、无痛和潜在更敏感的方法，用于检测癌症和密切监测个别患者对特定治疗的反应。

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.