THE BIOLOGY OF LUNG CANCER-- FDG AND FLUOROTHYMIDINE PET

本研究的目的是探讨定量[F-18]氟脱氧葡萄糖正电子发射断层扫描(PET)作为非小细胞肺癌(NSCLC)体内侵袭性的一种指标(即分级)，并与患者的预后以及先前被证明预测不良预后的标本衍生的细胞增殖指标(S期比例，Ki-67指数)进行比较。我们推测，在临床可切除的非小细胞肺癌患者中，术前FDG PET将显示具有更高FDG摄取的肿瘤：(A)手术切除后比同期低摄取的肿瘤更容易复发；(B)与相同临床分期但低摄取的肿瘤相比，更有可能发生纵隔或远处转移；(C)在其切除的标本中，Ki-67的S期比例更高。该提案的具体目标是：(1)进行全身FDG PET成像，并将原发性NSCLC的FDG摄取与预后相关。FDG摄入量将通过以下方法进行量化，这些方法将进行比较。标准摄取值(SUV)和SKM-FDGMR(用简化动力学方法测定FDG代谢率)。(2)术前行全身FDG PET显像，并将原发非小细胞肺癌的FDG摄取(量化为SUV和SKM-FDGMR)与PET和手术分期的病变程度进行相关性分析。(3)术前非小细胞肺癌的FDG摄取与切除标本中测量的细胞增殖标记物相关，以前的研究表明这些标记物可以预测不良预后。结果将通过无复发存活期、复发时间和存活率来衡量。总之，通过对非小细胞肺癌患者的术前研究，在任何形式的化疗或放射治疗之前，我们将获得关于肺癌生物学的宝贵信息，肺癌是美国癌症死亡的主要原因。通过使用FDGPET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预后会更差。这些信息将使个性化治疗成为可能。

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.