Lymphoma and Its Response to Treatment

非霍奇金淋巴瘤是一种由恶性B细胞淋巴细胞组成的肿瘤，具有不同的肿瘤分级和分期。治疗策略导致了高应答率，然而，最终三分之二的肿瘤变得对治疗产生抗药性，并是致命的。分子生物学的发展表明，淋巴瘤的恶性行为与细胞增殖增加和细胞死亡减少之间的平衡直接相关。最近，广泛使用的抗CD-20抗体在惰性淋巴瘤中表现出高水平的反应，没有化疗药物所观察到的毒性。抗CD-20抗体发挥治疗作用的机制存在争议，但可能与导致肿瘤的多种免疫学机制有关。 细胞死亡。对于更具侵袭性的肿瘤的治疗通常需要将抗CD-20抗体与传统的联合化疗方案(CHOP)相结合，这被认为具有协同效应。我们将调查生物特异性PET显像剂对评估整个疾病范围内淋巴瘤生物学活性的贡献。成像还将用于量化治疗反应的特定生物学方面。[C-11]-胸腺嘧啶核苷PET将用于提供肿瘤DNA合成的定量数据。我们将评估一种用于定量肿瘤细胞死亡的新的PET显像剂；[F-18]-Annexin V结合到暴露了因细胞程序性死亡而导致的磷脂酰丝氨酸残基的膜上。[C-11]-胸腺嘧啶核苷PET成像将被用来量化增殖，作为确定淋巴瘤部位的敏感试剂，并作为量化治疗反应的增长率基线。我们将使用[F-18]-Annexin V来量化治疗前、治疗期间和治疗后的肿瘤细胞死亡水平，并比较生长和死亡图像。图像性肿瘤 使用这些生物特异性试剂的摄取数据将与用于淋巴瘤临床诊断的临床参数相关，包括组织学类型、免疫表型、Bcl-2表达、血清LDH和β2微球蛋白。我们将使用流式细胞术对处于S期和单倍体型(正在经历细胞程序性死亡)的肿瘤细胞数量进行定量。这一新的成像信息将为通过不同的细胞毒性机制治疗淋巴瘤提供重要的洞察力，并设计更有效的治疗策略。

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.