Lymphoma and Its Response to Treatment

淋巴瘤及其对治疗的反应

• 批准号: 6984597
• 负责人: Janet F. Eary
• 金额: $ 9.35万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-10 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6984597
• 关键词: DNA replication; antineoplastics; antitumor antibody; bioimaging /biomedical imaging; biomarker; cell death; cell proliferation; clinical research; combination cancer therapy; flow cytometry; human subject; human therapy evaluation; image guided surgery /therapy; laboratory mouse; neoplasm /cancer chemotherapy; neoplasm /cancer immunotherapy; neoplastic growth; nonHodgkin' s lymphoma; patient oriented research; positron emission tomography; prognosis; radionuclides; DNA replication; antineoplastics; antitumor antibody; bioimaging /biomedical imaging; biomarker; cell death; cell proliferation; clinical research; combination cancer therapy; flow cytometry; human subject; human therapy evaluation; image guided surgery /therapy; laboratory mouse; neoplasm /cancer chemotherapy; neoplasm /cancer immunotherapy; neoplastic growth; nonHodgkin' s lymphoma; patient oriented research; positron emission tomography; prognosis; radionuclides

Non-Hodgkin's lymphoma is a tumor consisting of malignant B-cell lymphocytes that presents with a spectrum of tumor grades and stages. Treatment strategies result in high response rates, however, eventually two-thirds of all tumors become treatment resistant and are fatal. Developments in molecular biology have shown that lymphoma malignant behavior is directly related to the balance between increased cellular proliferation and decreased cell death. Recently, widespread use of anti-CD-20 antibody for indolent lymphomas has demonstrated high levels of response, without the toxicity observed with chemotherapeutic agents. The mechanisms through which anti-CD-20 antibodies exert their treatment effects are controversial, but probably relate to a variety of immunological mechanisms that result in induction of tumor cell death. Treatment for more aggressive tumors often involves a combination of anti-CD-20 antibody with the conventional combination chemotherapy regimen (CHOP), which is thought to exert a synergistic effect. We will investigate the contribution that biologically specific PET imaging agents can make to evaluation of lymphoma biological activity across the entire spectrum of disease. Imaging will also be used to quantitate specific biological aspects of response to therapy. [C-11]-Thymidine PET will be used to provide quantitative data on tumor DNA synthesis. We will evaluate a new PET imaging agent for quantitating tumor cell death; [F-18]-annexin V binds to membranes that have exposed phosphatidyl serine residues resulting from programmed cell death. [C-11]-thymidine PET imaging will be used to quantitate proliferation as a sensitive agent for identifying lymphoma sites and as a growth rate baseline for quantitating response to treatment. We will use [F-18]-annexin V to quantitate tumor levels of cell death prior to, during and after treatment and we will compare the growth and death images. Image-derived tumor uptake data using these biologically specific agents will be correlated with clinical parameters used in lymphoma clinical diagnosis including histologic type, immunophenotype, Bcl-2 expression, serum LDH and beta2 microglobulin. We will use flow cytometry to quantitate the population of tumor cells in S-phase and haploid type (undergoing programmed cell death). This new imaging information will provide critical insight into treatment effectiveness through different cytotoxic mechanisms for lymphoma treatment and to design of more effective treatment strategies.

非霍奇金的淋巴瘤是一种由恶性B细胞淋巴细胞组成的肿瘤，该淋巴细胞具有各种肿瘤成绩和阶段。但是，治疗策略导致高反应率最终，最终所有肿瘤中有三分之二变得耐药性并且致命。分子生物学的发展表明，淋巴瘤恶性行为直接与细胞增殖与细胞死亡减少之间的平衡有关。最近，抗CD-20抗体对不变淋巴瘤的广泛使用表现出很高的反应，没有化学治疗剂的毒性。抗CD-20抗体发挥其治疗作用的机制是有争议的，但可能与多种免疫机制有关，这些机制导致诱导肿瘤 细胞死亡。更具攻击性肿瘤的治疗通常涉及将抗CD-20抗体与常规组合化疗方案（CHOP）组合，这被认为具有协同作用。我们将调查以下贡献，即生物学特有的宠物成像剂可以评估整个疾病范围内淋巴瘤生物学活性。成像还将用于量化对治疗反应的特定生物学方面。 [C-11] - 胸腺苷PET将用于提供有关肿瘤DNA合成的定量数据。我们将评估一种新的宠物成像剂来定量肿瘤细胞死亡； [F-18] -Annexin V与膜导致的磷脂酰丝氨酸残基导致了编程细胞死亡。 [C-11] - 胸腺苷PET成像将用于定量增殖，作为识别淋巴瘤部位的敏感剂，并作为定量对治疗反应的生长速率基线。我们将使用[F-18] -Annexin V来定量治疗之前和之后的细胞死亡水平，我们将比较生长和死亡图像。图像衍生的肿瘤 使用这些生物学特异性药物的吸收数据将与淋巴瘤临床诊断中使用的临床参数相关，包括组织学类型，免疫表型，BCL-2表达，血清LDH和Beta2微果蛋白。我们将使用流式细胞仪来定量S期和单倍体类型（经过编程细胞死亡）中的肿瘤细胞种群。这种新的成像信息将通过不同的细胞毒性机制来为淋巴瘤治疗和设计更有效的治疗策略提供对治疗有效性的关键见解。