QUANTITATION OF TUMOR GROWTH IN NOVEL CANCER THERAPIES

[C-11]胸苷已被证明是一种敏感且特异的药物 观察肿瘤对治疗的反应。 PET用放射性药物 成像旨在提供肿瘤 DNA 合成的定量数据 率。我们已将成像和血液采样数据纳入动力学中 DNA 代谢模型，用于生成参数图像 肿瘤中的胸苷通量率。随着我们在以下方面取得实质性进展 为了验证这个过程，我们将使用[C-11]胸苷作为工具 观察癌症治疗中的肿瘤反应。在具体目标 1a 中，患者 将研究接受标准治疗的脑肿瘤。程度 用胸苷测定肿瘤渗透到正常大脑的程度 通量图像。这些图像将区分在 血脑破坏和增殖性肿瘤导致的 MR 或 CT 成像 扩展。 [F-18]FDG 成像将提供肿瘤之间的比较 新陈代谢和增殖。具体目标 2 将测量肿瘤的变化 接受化疗的乳腺癌患者的增殖 [c-11]胸苷。化疗药物对于以下疾病非常有效 但毒性极大。时间和范围 反应未知。这组患者将使用 [C- 11] 胸苷治疗前后：1) 通过以下方式分析反应者 胸苷摄取与肿瘤活检的相关性，2）观察时间- 应答和应答中胸苷摄取的变化过程 患者。与目标 1 一样，FDG 图像将在相同的时间点获得 比较用胸苷测量的肿瘤代谢和增殖。 将 [C-11] 胸苷与 [F-18]FDG 结合使用并进行活检分析 材料，我们将获得关于范围和程度的宝贵见解 脑肿瘤和乳腺癌对治疗策略的反应。聚酯 使用这些药物的代谢成像可以对肿瘤进行全面的成像 随着时间的推移进行体内评估，将有助于更好的患者 管理以及更好地了解肿瘤生物学。

[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.