QUANTITATION OF TUMOR GROWTH IN NOVEL CANCER THERAPIES

[C-11]胸腺嘧啶核苷已被证明是一种敏感和特异的药物 观察肿瘤对治疗的反应。用于正电子发射断层扫描的放射性药物 成像的目的是提供有关肿瘤DNA合成的定量数据 费率。我们已经将成像和血液采样数据整合到了Kinetic 用于生成参数图像的DNA新陈代谢模型 肿瘤组织中的胸腺嘧啶核苷流量。继我们在以下方面取得实质性进展后 为了验证这一过程，我们将使用[C-11]胸腺嘧啶核苷作为工具 观察肿瘤在癌症治疗中的反应。在特定的目标1a中，患者 将对接受标准治疗的脑瘤进行研究。广度 肿瘤对正常脑组织的渗透率将通过胸腺嘧啶核苷来确定 通量图像。这些图像将区分在 血脑破裂和增生性肿瘤的MR或CT成像 分机。[F-18]FDG成像将提供肿瘤之间的比较 新陈代谢和增殖。特定目标2将测量肿瘤的变化 联合化疗对乳腺癌患者增殖的影响 [C-11]胸苷。化疗药物对癌症非常有效。 百分比的患者，但毒性极大。时间和程度 反应未知。这组患者将接受[C-]成像 11]治疗前和治疗后的胸腺嘧啶核苷：1)通过 胸腺嘧啶核苷摄取与肿瘤活检的相关性及2)观察胸腺嘧啶核苷摄取的时间 应答和应答时胸腺嘧啶核苷摄取的变化过程 病人。与目标1一样，将在相同的时间点获得FDG图像 比较胸腺嘧啶核苷测定的肿瘤代谢和增殖情况。 [C-11]胸腺嘧啶核苷与[F-18]FDG联合应用及活检检测 材料，我们将获得有价值的洞察力 脑瘤和乳腺癌对治疗策略的反应。宠物 用这些试剂进行代谢成像可以使全面的肿瘤 随着时间的推移进行体内评估，并将有助于改善患者 管理以及对肿瘤生物学的更好理解。

[C-11]Thymidine has been shown to be a sensitive and specific agent for observing tumor response to treatment. The radiopharmaceutical for PET imaging is designed to provide quantitative data on tumor DNA synthetic rate. We have incorporated imaging and blood sampling data into kinetic models od DNA metabolism that are used to generate parametric images of thymidine flux rate in tumor. Following our substantial progress in validating this procedure, we will use [C-11]thymidine as a tool to observe tumor response in cancer therapy. In Specific Aim 1a, patients with brain tumors undergoing standard therapy will be studied. The extent of tumor penetration into normal brain will be determined with thymidine flux images. These images will distinguish between abnormalities seen on MR or CT imaging due to blood-brain disruption and proliferative tumor extension. Imaging with [F-18]FDG will provide a comparison between tumor metabolism and proliferation. Specific Aim 2 will measure changes in tumor proliferation in patients with breast cancer undergoing chemotherapy using [c-11]thymidine. Chemotherapeutic agents are highly effective for a percentage of patients but are extremely toxic. The timing and extent of response are unknown. This group of patients will be imaged with [C- 11]thymidine before and after treatment to: 1) profile responders by correlation of thymidine uptake with tumor biopsy and 2) observe the time- course of change in thymidine uptake in responding and on-responding patients. As in Aim 1, FDG images will be obtained at the same timepoints to compare tumor metabolism and proliferation measured with thymidine. Using [C-11]thymidine in association with [F-18]FDG and assays on biopsy material, we will gain valuable insight into the extent and magnitude of response of brain tumors and breast cancer to treatment strategies. PET metabolic imaging with these agents can make comprehensive tumor assessments in vivo over time and will contribute to better patient management as well as better understanding of tumor biology.