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）作为体内非小细胞肺癌（NSCLC）侵袭性的指标（即分级），并与患者结局和先前显示可预测不良结局的细胞增殖指标（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吸收较高的肿瘤：（a）在手术切除后比低吸收的同分期肿瘤更快复发;（b）与相同临床分期但低吸收的肿瘤相比，更有可能患有纵膈或远端转移性疾病;（B）切除标本中Ki-67评分的S期分数较高。该提案的具体目标是：（1）进行全身术前FDG PET成像，并将原发性NSCLC的FDG摄取与结局相关联。FDG摄取将通过以下方法进行定量，并进行比较。标准化摄取值（SUV）和SKM-FDGMR（通过简化动力学方法测定的FDG代谢率）。(2)进行全身术前FDG PET成像，并将原发性NSCLC中的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)将原发性非小细胞肺癌术前FDG摄取与从切除标本中测量的细胞增殖标记物相关联，并且先前显示预测不良结局。结果将通过无复发生存期、复发时间和生存期来衡量。总之，通过在术前研究NSCLC患者，在任何形式的化疗或放疗之前，我们将获得关于肺癌生物学的有价值的信息，肺癌是美国癌症死亡的主要原因。通过使用FDG PET对可切除的非小细胞肺癌进行生物学分级，我们将预测哪些患者的结局会更差。这些信息将允许个性化治疗。

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.