THE BIOLOGY OF LUNG CANCER-- FDG AND FLUOROTHYMIDINE PET

拟议研究的目的是研究定量[F- 18]氟脱氧葡萄糖（FDG）正电子发射断层扫描（PET）作为非小细胞肺癌（NSCLC）体内侵袭性（即分级）的测量方法，并与患者结果和先前显示预测不良结果的标本来源的细胞增殖测量方法（s期分数，Ki-67指数）进行比较。我们假设，在临床可切除的非小细胞肺癌患者中，术前FDG PET将显示FDG摄取较高的肿瘤：(a)手术切除后比低摄取的同期肿瘤复发更快；(b)与相同临床分期但摄取低的肿瘤相比，更有可能患有纵隔或远端转移性疾病；(c)切除标本中Ki-67分数的s相分数较高。该建议的具体目的是：(1)术前进行全身FDG PET成像，并将原发性NSCLC中FDG摄取与结果联系起来。FDG摄取将通过以下方法进行量化，并进行比较。标准化摄取值（SUV）和SKM-FDGMR（通过简化动力学方法确定的FDG代谢率）。(2)术前进行全身FDG PET成像，并将原发性NSCLC的FDG摄取（量化为SUV和SKM-FDGMR）与PET和手术分期显示的疾病程度相关联。(3)将原发性NSCLC术前FDG摄取与从切除标本中测量的细胞增殖标志物相关联，这些标志物先前被证明可以预测不良预后。结果将通过无复发生存、复发时间和生存来衡量。总之，在任何形式的化疗或放疗之前，通过对非小细胞肺癌患者进行术前研究，我们将获得有关肺癌生物学的宝贵信息，肺癌是美国癌症死亡的主要原因。通过FDG PET对可切除的NSCLC进行生物学分级，我们将预测哪些患者的预后更差。这些信息将允许个体化治疗。

The objective of the proposed studies is to investigate quantitative [F- 18]fluorodeoxyglucose (FDG) Positron Emission Tomography (PET) as a measure of non-small cell lung cancer (NSCLC) aggressiveness in vivo (i.e. grading) and to make comparisons with patients' outcomes and with specimen-derived measures of cellular proliferation previously shown to predict poor outcome (S-phase fraction, Ki-67 index). We postulate that, in clinically resectable NSCLC patients, pre-operative FDG PET will show that tumors with higher FDG uptake: (a) will recur sooner after surgical resection than same stage tumors with low uptake; (b) are more likely to have mediastinal or distal metastatic disease than tumors of the same clinical stage but low uptake; (c) have higher S-phase fraction of Ki-67 scores in their resected specimen. The specific aims of the proposal are: (1) Perform whole-body pre- operative FDG PET imaging and correlate FDG uptake in primary NSCLC with outcome. FDG uptake will be quantified by the following methods that will be compared. Standardized Uptake Value (SUV) and SKM-FDGMR (FDG Metabolic Rate determined by a Simplified Kinetic Method). (2) Perform whole-body pre-operative FDG PET imaging and correlate FDG uptake (quantified as SUV and SKM-FDGMR) in primary NSCLC with disease extent as demonstrated by PET and surgical staging. (3) Correlate pre-operative FDG uptake in primary NSCLC with markers of cellular proliferation measured from the resected specimen and previously shown to predict poor outcome. Outcome will be measured by recurrence-free survival, time-to recurrence and survival. In summary, by studying NSCLC patients pre-operatively, prior to any form of chemotherapy or radiotherapy, we will gain valuable information about the biology of lung cancer, the leading cause of cancer death in the United States. By performing a biologic grading of resectable NSCLC with FDG PET, we will predict which patients will have a worse outcome. This information will allow individualized therapy.