Light Scatter In Vivo Flow Cytometry to Monitor Cancer

描述（由申请人提供）：该R21/R33联合提案的主要目标是开发和评估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（包括癌细胞和白细胞）的新方法。如果成功，LSIVFC将在癌症患者群体的临床管理中有重要的应用，作为一种非侵入性的方法：A)检测循环癌细胞，这可能对癌症治疗后微小残留疾病的检测特别有用；b)监测化学预防、光动力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，该项目涉及科学家和临床医生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的专业知识的密切合作。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，以优化检测不同的感兴趣的血细胞群体，如癌细胞和白细胞（wbc） （Aim 1）。该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，我们将对少量动物进行测量，以说明LSIVFC研究用于监测循环癌症和白细胞的可行性（目的3）。在R33期，我们将开发和优化该技术用于体内数据采集和分析（Aims 1和5），我们将说明LSIVFC在疾病进展和治疗反应（Aim 2）、骨髓移植（Aim 3）和白细胞激活（Aim 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。这一建议与改善公共卫生，特别是对癌症患者的护理高度相关。开发一种监测循环白细胞和癌细胞的非侵入性方法，将提供一种非侵入性、无痛且可能更敏感的方法来检测癌症，并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.