非小细胞肺癌VEGF表达与PET/CT显像的相关性研究
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摘要
目的:1.研究非小细胞肺癌患者~(18)F-FDG PET/CT的显像特点。2.探讨非小细胞肺癌组织VEGF表达与~(18)F-FDG摄取之间的关系。3.研究非小细胞肺癌患者血清VEGF水平与~(18)F-FDG PET/CT显像的关系。
     方法:1.PET/CT显像与非小细胞肺癌组织VEGF表达间关系的研究:40例非小细胞肺癌患者,其中腺癌14例、鳞癌20例、腺鳞癌4例、肺泡癌2例,均行全身PET/CT显像检查,并取术后肿块组织作VEGF免疫组化检测。另有15例肺部良性病变患者作为对照组,同样条件下行全身PET/CT显像检查和取术后肿块组织作VEGF免疫组化检测。采用Mattern半定量分析方法,对肿块组织VEGF表达进行总评分。测定所有PET/CT显像者的SUV,分别对肺部良、恶性病变和不同病理类型的非小细胞肺癌的SUV进行比较;并分别对肺部良、恶性病变肿块组织VEGF表达评分、非小细胞肺癌组织VEGF表达评分与SUV相关性进行统计学分析。
     2.PET/CT显像与非小细胞肺癌患者血清VEGF表达间关系的研究:40例非小细胞肺癌患者(鳞癌19例、腺癌19例、肺泡癌2例)、20例肺部良性病变患者(良性对照组)均行全身PET/CT显像检查和血清VEGF检测,并检测20例健康体检者的血清VEGF水平作为血清VEGF的健康对照。分别对非小细胞肺癌组与健康对照组和肺部良性病变组血清VEGF水平进行比较,对肺鳞癌、腺癌的血清VEGF水平进行比较,并对非小细胞肺癌患者血清VEGF的表达与肿块SUV的相关性、非小细胞肺癌患者血清VEGF表达与PET/CT的T分期和N分期关系进行统计学分析,以及对非小细胞肺癌患者有、无远处转移者的血清VEGF表达进行比较。
     结果:1.80例非小细胞肺癌患者平均SUV(4.50±2.78)明显高于35例良性病变组(2.05±0.63),p<0.05。
     2.对20例肺鳞癌、14例腺癌、7例炎性假瘤的肿块组织VEGF表达评分进行分析,发现三者之间VEGF表达评分比较无明显统计学差异,P值均>0.05;8例肺结核瘤与前三组比较有统计学差异,P值均<0.05。
     3.40例非小细胞肺癌组织VEGF表达与SUV显著相关,VEGF评分越高,SUV越高,r=0.478,P<0.01。术后随访病例中半年内复发组VEGF评分也明显高于未复发组。
     4.非小细胞肺癌患者血清VEGF水平为600.27±324.73 pg/mL,明显高于健康对照组血清VEGF水平176.75±109.85 pg/mL和良性病变组水平290.55±144.90pg/mL,P<0.05。
     5.非小细胞肺癌患者血清VEGF水平与肿块SUV显著相关,VEGF水平越高,SUV越高,r=0.609,P<0.01。
     6.按照PET/CT检查结果将40例非小细胞肺癌患者进行T、N、M分期。T分期中T1期组与T3期、T4期组之间,T2期组与T4期组之间血清VEGF表达水平均有统计学差异,P值均<0.05;N分期中SUV≥2.5组和SUV<2.5组之间血清VEGF表达水平有统计学差异(t=2.53,P<0.05);M分期中有远处转移组和无远处转移组之间血清VEGF表达水平有统计学差异(t=-3.20,P<0.05)。
     结论:1.非小细胞肺癌患者的~(18)F-FDG SUV与肿瘤组织VEGF表达评分呈正相关,测定SUV对于预测非小细胞肺癌肿瘤组织中血管增生情况具有重要的临床价值。
     2.非小细胞肺癌组织中VEGF表达越高,其术后发生复发和/或转移的可能性越大。VEGF表达评分可考虑作为患者预后和近期复查的参考指标。
     3.按T、N、M分期进行分组的不同非小细胞肺癌患者血清VEGF水平均有统计学差异,检测血清VEGF在一定程度上可预测非小细胞肺癌的临床分期并进行预后。
Objective:1.To evaluate the character of ~(18)F-FDG PET/CT imagingin patients with NSCLC.2.To probe the association betweeen ~(18)F-FDG absortion and the expression level of VEGF in NSCLC.3.To evaluate the relationship between serum level of VEGF and ~(18)F-FDG PET/CT imaging.
     Methods: 1.40 patients were enrolled including 20 squamous cell carcinoma, 14 adeno carcinoma, 4 bronchial alveolar carcinoma and 4 adenosquamous carcinoma ;another,15 patients with benign lesion were enrolled including 8 tuberculoma and 7 inflammatory pseudotumor. All the patients were taken the ~(18)F-FDG PET/CT imaging of the whole body before operation,then the tumor tissue was obtained after the operation. The VEGF expression status was measured by SABC method, the half-quantitation score of the VEGF expression was taken by mattern analysis.
     2.40 patients were enrolled including 19 squamous cell carcinoma, 19 adenocarcinoma and 2 bronchial alveolar carcinoma; Another 20 patients with benign lesion were enrolled including 12 tuberculoma,2 pulmonary infection,4 inflammatory pseudotumor and 2 pneumosilicosis.
     The serum of patients was collected before the ~(18)F-FDG PET/CT imaging, the srum level of the VEGF examined by ELISA method.
     Results: 1.The average SUV was significantly higher in patients with NSCLC group than in patients with benign lesion .(p<0.05).
     2.The half-quantitation score of the VEGF expression have no significantly difference in the squamous cell carcinoma, adenocarcinoma and inflammatory pseudotumor. The score of the VEGF expression was significantly lower in tumor tissue of tuberculoma than in tumor tissue of squamous cell carcinoma and adenocarcinoma.
     3.There was a significant correlation between VEGF expression of carcinoma tissue and SUV of ~(18)F-FDG,(r=0.478,P<0.01). Futher more,the score of the VEGF expression was significantly higher in patients with metastasis and/or recurrence after operation than in Patients with no metastasis and/or recurrence.
     4.The serum level of VEGF was significantly higher in patients with NSCLC than in control group and in patients with benign lesion (P<0.05).
     5.There was a significant correlation between serum level of VEGF and SUV of ~(18)F-FDG(r=0.609,P<0.01).
     6. According to the results of PET/CT imaging. There was a significantly correlation between serum level of VEGF and clinical stage. Conclusion:1.There was a significant correlation between the SUV of ~(18)F-FDG and VEGF expression of carcinoma tissue, the determination of SUV may be predict clinical value of the vascular proliferation incarcinoma tissue.
     2.The score of VEGF expression was significantly higher in patients with metastasis and/or recurrence after operation than in Patients with no metastasis and/or recurrence. The score of the VEGF expression may be considered as a screening index of the patients,whether they should recheck or not after operation.
     3.There was a significant correlation between serum level of VEGFand clinical stage.Serum level of VEGF may be regarded as a prognosticfactor in lung cancer.
引文
[1] Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2007. CA Cancer J Clin JT - CA: a cancer journal for clinicians, 2007, 57: 43-66.
    [2] Schafers KP, Stegger L. Combined imaging of molecular function and morphology with PET/CT and SPECT/CT: Image fusion and motion correction. Basic Res Cardiol, 2008,103: 191-199.
    [3] Sharma V, Luker GD, Piwnica-Worms D. Molecular imaging of gene expression and protein function in vivo with PET and SPECT. J Magn Reson Imaging, 2002, 16:336-351.
    [4] Pedersen MW, Holm S, Lund EL, et al. Coregulation of glucose uptake and vascular endothelial growth factor (VEGF) in two small-cell lung cancer (SCLC) sublines in vivo and in vitro. Neoplasia, 2001, 3: 80-87.
    [5] Higashi K, Ueda Y, Sakurai A, et al. Correlation of Glut-1 glucose transporter- expression with F- FDG uptake in non-small cell lung cancer.Eur J Nucl Med.2000,27: 1778-1785.
    
    [6] Chung JK, Lee YJ, Kim C, et al. Mechanisms related to ~(18)F-fluoro deoxy glucoseu ptake of human colon cancer stransplanted in nudem ice.J N ucl Med 1999, 40: 339-346.
    [7] Kuhn H, Hammerschmidt S, Wirtz H. Targeting tumorangiogenesis in lung cancer by suppression of VEGF and its receptor - results from clinical trials and novel experimental approaches. Curr Med Chem, 2007, 14: 3157-3165.
    [8] Zhao J, Liu XY, Zhang QY, et al. [Plasma level and prognostic significance of VEGF, bFGF and MMP-9 in patients with advanced non-small-cell lung cancer]. Zhonghua Zhong Liu Za Zhi, 2005,27: 676-679.
    [9] Seto T, Higashiyama M, Funai H, et al. Prognostic value of expression of vascular endothelial growth factor and its flt-1 and KDR receptors in stage I non-small-cell lung cancer. Lung Cancer, 2006, 53: 91-96.
    [10]Tas F, Duranyildiz D, Oguz H, et al. Serum vascular endothelial growth factor (VEGF)and bcl-2 levels in advanced stage non-small cell lung cancer.Cancer Invest,2006,24:576-580.
    [11]Ghio P,Cappia S,Selvaggi G,et al.Prognostic role of protease-activated receptors 1 and 4 in resected stage IB non-small-cell lung cancer.Clin Lung Cancer,2006,7:395-400.
    [12]Vansteenkiste JF,Schildermans RH.The future of adjuvant chemotherapy for resected non-small cell lung cancer.Expert Rev Anticancer Ther,2005,5:165-175.
    [13]Ludwig GS,AntoniaDS,Dirk K,et al.~(18)F-FDG kinetics and gene expresSsion in giant cell tumors 〔J〕 1J NuclearMed,2004;45(9):1528-1531.
    [14]李冬.非小细胞肺癌VEGF表达与SUV值的相关性研究[J].中国老年学杂志,2008,2:298-299.
    [15]Montain CF,,Dresler CM.Revisions in the international system for staging lung cancer.chest,1997,111:1710.
    [16]Matern J,Koomagi R,Volm M,et al.Vascular endothelial growth factor experssion angiogenesis in non-small cell lung carcinomas.Int J Oncol,1995,6:1059-1062.
    [17]Hashimoto Y,Tsujikawa T,Kondo C,et al.Accuracy of PET for diagnosis of solid pulmonary lesions with 18F-FDG uptake below the standardized uptake value of 2.5.J Nucl Med,2006,47:426-431.
    [18]Orlacchio A,Schillaci O,Antonelli L,et al.Solitary pulmonary nodules:morphological and metabolic characterisation by FDG-PET-MDCT.Radiol Med (Torino),2007,112:157-173.
    [19]Higashi T,Saga T,Nakamoto Y,et al.Relationship between retention index in dual-phase(18)F-FDG PET,and hexokinase-Ⅱ and glucose transporter-1expression in pancreatic cancer.J Nucl Med,2002,43:173-180.
    [20]Riedl CC,Akhurst T,Larson S,et al.18F-FDG PET scanning correlates with tissue markers of poor prognosis and predicts mortality for patients after liver resection for colorectal metastases.J Nucl Med,2007,48:771-775.
    [21]Wang T,Sun YE,Yao SL,et al.[Relationship between overexpression of facilitative glucose transporter-1 and fluorodeoxyglucose uptake in primary human lung adenocarcinoma]. Zhonghua Wai Ke Za Zhi, 2004, 42: 968-971.
    [22]Kamiyama Y, Aihara R, Nakabayashi T, et al. 18F-fluorodeoxyglucose positron emission tomography: useful technique for predicting malignant potential of gastrointestinal stromal tumors. World J Surg, 2005,29: 1429-1435.
    [23] Mamede M, Higashi T, Kitaichi M, et al. [18F]FDG uptake and PCNA, Glut-1, and Hexokinase-II expressions in cancers and inflammatory lesions of the lung. Neoplasia, 2005, 7: 369-379.
    [24] Buck AK, Halter G, Schirrmeister H, et al. Imaging proliferation in lung tumors with PET: 18F- FLT versus 18F-FDG. J Nucl Med, 2003,44:1426-1431.
    [25] Grothey A. Future directions in vascular endothelial growth factor-targeted therapy for metastatic colorectal cancer. Semin Oncol, 2006, 33: S41-49.
    [26] Kyzas PA. El-Gazzar R, Macluskey M, Williams H, Ogden GR. Vascularity and expression of vascular endothelial growth factor in oral squamous cell carcinoma, resection margins, and nodal metastases. Br J Oral Maxillofac Surg 2006; 44: 193-197 [Epub 2005, August 10]. Br J Oral Maxillofac Surg, 2007, 45: 345; author reply 343-344.
    [27] Woo IS, Kim KA, Jeon HM, et al. Pretreatment serum endostatin as a prognostic indicator in metastatic gastric carcinoma. Int J Cancer, 2006,119: 2901-2906.
    [28] Ohta Y, Tanaka Y, Watanabe G, et al. Predicting recurrence following curative surgery in stage I non-small cell lung cancer patients using an angiogenesis-associated factor. J Exp Clin Cancer Res, 2007,26: 301-305.
    [29] Avril N, Menzel M, Dose J, et al. Glucose metabolism of breast cancer assessed by 18F-FDG PET: histologic and immunohistochemical tissue analysis. J Nucl Med, 2001,42: 9-16.
    [30] Bos R, van Der Hoeven JJ, van Der Wall E, et al. Biologic correlates of (18)fluorodeoxyglucose uptake in human breast cancer measured by positron emission tomography. J Clin Oncol, 2002, 20: 379-387.
    [31] Zasadny KR, Tatsumi M, Wahl RL. FDG metabolism and uptake versus blood flow in women with untreated primary breast cancers. Eur J Nucl Med Mol Imaging, 2003, 30: 274-280.
    [32]Gasparini G, Toi M, Gion M, et al. Prognostic significance of vascular endothelial growth factor protein in node-negative breast carcinoma. J Natl Cancer Inst, 1997, 89: 139-147.
    [33] Cheung CY. Vascular endothelial growth factor activation of intramembranous absorption: a critical pathway for amniotic fluid volume regulation. J Soc Gynecol Investig, 2004, 11: 63-74.
    [34]Tamura M, Ohta Y, Kajita T, et al. Plasma VEGF concentration can predict the tumor angiogenic capacity in non-small cell lung cancer. Oncol Rep, 2001, 8: 1097-1102.
    [35]Minami K, Saito Y, Imamura H, et al. Prognostic significance of p53, Ki-67, VEGF and Glut-1 in resected stage I adenocarcinoma of the lung. Lung Cancer, 2002,38:51-57.
    [36]Ribatti D, Marimpietri D, Pastorino F, et al. Angiogenesis in neuroblastoma. Ann N YAcad Sci, 2004, 1028: 133-142.
    [37]Han H, Silverman JF, Santucci TS, et al. Vascular endothelial growth factor expression in stage I non-small cell lung cancer correlates with neoangiogenesis and a poor prognosis. Ann Surg Oncol, 2001, 8: 72-79.
    [38] Zaman K, Driscoll R, Hahn D, et al. Monitoring multiple angiogenesis-related molecules in the blood of cancer patients shows a correlation between VEGF-A and MMP-9 levels before treatment and divergent changes after surgical vs. conservative therapy. Int J Cancer, 2006,118: 755-764.
    [39]Laack E, Scheffler A, Burkholder I, et al. Pretreatment vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) serum levels in patients with metastatic non-small cell lung cancer (NSCLC). Lung Cancer, 2005, 50: 51-58.
    [40]Bolat F, Kayaselcuk F, Nursal TZ, et al. Microvessel density, VEGF expression, and tumor-associated macrophages in breast tumors: correlations with prognostic parameters. J Exp Clin Cancer Res, 2006, 25: 365-372.
    [1]Jemal A,Siegel R,Ward E,et al.Cancer statistics,2007.CA Cancer J Clin JT-CA:a cancer journal for clinicians,2007,57:43-66.
    [2]Parkin DM,Bray FI,Devesa SS.Cancer burden in the year 2000.The global picture.Eur J Cancer JT-European journal of cancer(Oxford,England:1990),2001,37 Suppl 8:S4-66.
    [3]Buccheri G,Ferrigno D.Prognostic value of stage grouping and TNM descriptors in lung cancer.Chest JT-Chest,2000,117:1247-1255.
    [4]Kelsey CR,Light KL,Marks LB.Patterns of failure after resection of non-small-cell lung cancer:implications for postoperative radiation therapy volumes.Int J Radiat Oncol Biol Phys JT-International journal of radiation oncology,biology,physics,2006,65:1097-1105.
    [5]Mac Manus MP,Hicks RJ,Matthews JP,et al.Positron emission tomography is superior to computed tomography scanning for response-assessment after radical radiotherapy or chemoradiotherapy in patients with non-small-cell lung cancer.J Clin Oncol JT-Journal of clinical oncology:official journal of the American Society of Clinical Oncology,2003,21:1285-1292.
    [6] Vansteenkiste J, Fischer BM, Dooms C, et al. Positron-emission tomography in prognostic and therapeutic assessment of lung cancer: systematic review. Lancet Oncol JT - The lancet oncology, 2004, 5: 531-540.
    [7] Jager PL, Vaalburg W, Pruim J, et al. Radiolabeled amino acids: basic aspects and clinical applications in oncology. J Nucl Med JT - Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2001,42: 432-445.
    [8] Kracht LW, Miletic H, Busch S, et al. Delineation of brain tumor extent with [11C]L-methionine positron emission tomography: local comparison with stereotactic histopathology. Clin Cancer Res JT-Clinical cancer research: an official journal of the American Association for Cancer Research, 2004, 10: 7163-7170.
    [9] Eschmann SM, Pfannenberg AC, Rieger A, et al. Comparison of 11C-choline-PET/CT and whole body-MRI for staging of prostate cancer. Nuklearmedizin JT - Nuklearmedizin. Nuclear medicine, 2007, 46: 161-168; quiz N47-48.
    [10]Utriainen M, Komu M, Vuorinen V, et al. Evaluation of brain tumor metabolism with [11CJcholine PET and 1H-MRS. J Neurooncol JT- Journal of neuro-oncology, 2003, 62: 329-338.
    [11]de Jong IJ, Pruim J, Elsinga PH, et al. 11C-choline positron emission tomography for the evaluation after treatment of localized prostate cancer. Eur Urol JT- European urology, 2003,44: 32-38; discussion 38-39.
    [12] Zheng QH, Gao M, Mock BH, et al. Synthesis and biodistribution of new radiolabeled high-affinity choline transporter inhibitors [11C]hemicholinium-3 and [18F]hemicholinium-3. Bioorg Med Chem Lett JT- Bioorganic & medicinal chemistry letters, 2007, 17: 2220-2224.
    [13]Nanni C, Zamagni E, Cavo M, et al. 11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma. World J Surg Oncol JT-World journal of surgical oncology, 2007, 5:68.
    [14] Zhao S, Kuge Y, Kohanawa M, et al. Usefulness of 11C-methionine for differentiating tumors from granulomas in experimental rat models: a comparison with 18F-FDG and 18F-FLT.J Nucl Med JT - Journal of nuclear medicine:official publication,Society of Nuclear Medicine,2008,49:135-141.
    [15]Chao KS.3 '-deoxy-3'-(18)F-fluorothymidine(FLT)positron emission tomography for early prediction of response to chemoradiotherapy--a clinical application model of esophageal cancer.Semin Oncol JT-Seminars in oncology,2007,34:S31-36.
    [16]马寄晓,叶大铸.奥曲肽及其类似物用于肿瘤治疗的进展[J].国外医学 放射医学核医学分册,2005,29(2):79-84.
    [17]王荣福,刘萌.放射性Annexin V活体细胞凋亡显像在肿瘤应用研究及进展[J].中国医学影像技术杂志,2004,20(10):1616-1619.
    [18]Collingridge DR,Glaser M,Osman S,et al.In vitro selectivity,in vivo biodistribution and tumour uptake of annexin V radiolabelled with a positron emitting radioisotope.Br J Cancer JT-British journal of cancer,2003,89:1327-1333.
    [19]Keen HG,Dekker BA,Disley L,et al.Imaging apoptosis in vivo using 124I-annexin V and PET.Nucl Med Biol JT - Nuclear medicine and biology,2005,32:395-402.
    [20]Lendvai G,Velikyan I,Bergstrom M,et al.Biodistribution of 68Ga-labelled phosphodiester,phosphorothioate,and 2'-O-methyl phosphodiester oligonuc -leotides in normal rats.Eur J Pharm Sci JT - European journal of pharmaceutical sciences:official journal of the European Federation for Pharmaceutical Sciences,2005,26:26-38.
    [21]Roivainen A,Tolvanen T,Salomaki S,et al.68Ga-labeled oligonucleotides for in vivo imaging with PET.J Nucl Med JT - Journal of nuclear medicine:official publication,Society of Nuclear Medicine,2004,45:347-355.
    [22]钱桂生.肺癌的诊断与治疗进展[J].临床内科杂志,2002,19(5):323-325.
    [23]Weng E,Tran L,Rege S,et al.Accuracy and clinical impact of mediastinal lymph node staging with FDG-PET imaging in potentially resectable lung cancer.Am J Clin Oncol JT- American journal of clinical oncology,2000,23:47-52.
    [24]Reed CE,Harpole DH,Posther KE,et al.Results of the American College of Surgeons Oncology Group Z0050 trial: the utility of positron emission tomography in staging potentially operable non-small cell lung cancer. J Thorac Cardiovasc Surg JT- The Journal of thoracic and cardiovascular surgery, 2003,126: 1943-1951.
    [25] Pass HI. Mediastinal staging 2005: pictures, scopes, and scalpels. Semin Oncol JT - Seminars in oncology, 2005, 32: 269-278.
    [26] Quint LE. Staging non-small cell lung cancer. Cancer Imaging JT - Cancer imaging : the official publication of the International Cancer Imaging Society, 2007, 7: 148-159.
    [27]Cerfolio RJ, Ojha B, Bryant AS, et al. The role of FDG-PET scan in staging patients with nonsmall cell carcinoma. Ann Thorac Surg JT - The Annals of thoracic surgery, 2003, 76: 861-866.
    [28] Bury T, Paulus P, Dowlati A, et al. Staging of the mediastinum: value of positron emission tomography imaging in non-small cell lung cancer. Eur Respir J JT - The European respiratory journal: official journal of the European Society for Clinical Respiratory Physiology, 1996, 9: 2560-2564.
    [29]Borrego Dorado I, Lopez Garcia C, Vazquez Albertino R, et al. [Evaluation of efficacy and clinical impact of FDG-PET on patients with potentially resectable non-small cell lung cancer]. Rev Esp Med Nucl JT - Revista espanola de medicina nuclear, 2007, 26: 335-344.
    [30]Posther KE, McCall LM, Harpole DH Jr, et al. Yield of brain 18F-FDG PET in evaluating patients with potentially operable non-small cell lung cancer. J Nucl Med JT - Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2006, 47: 1607-1611.
    [31]Hellwig D, Graeter TP, Ukena D, et al. Value of F-18-fluorodeoxyglucose positron emission tomography after induction therapy of locally advanced bronchogenic carcinoma. J Thorac Cardiovasc Surg, 2004, 128: 892-899.
    [32]Hoekstra CJ, Stroobants SG, Smit EF, et al. Prognostic relevance of response evaluation using [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography in patients with locally advanced non-small-cell lung cancer. J Clin Oncol, 2005, 23: 8362-8370.
    [33]Mac Manus MP, Hicks RJ, Matthews JP, et al. Positron emission tomography is superior to computed tomography scanning for response-assessment after radical radiotherapy or chemoradiotherapy in patients with non-small-cell lung cancer. J Clin Oncol, 2003, 21: 1285-1292.
    [34]Hicks RJ, Kalff V, MacManus MP, et al. The utility of F-FDG PET for suspected recurrent non-small cell lung cancer after potentially curative therapy: impact on management and prognostic stratification. J Nucl Med. 2001; 42: 1605-1613.
    [35]Schrevens L, Lorent N, Dooms C, et al. The role of PET scan in diagnosis, staging, and management of non-small cell lung cancer. Oncologist JT- The oncologist, 2004, 9: 633-643.
    [36]Hensing TA. Clinical evaluation and staging of patients who have lung cancer. Hematol Oncol Clin North Am JT - Hematology/oncology clinics of North America, 2005,19:219-235.
    [37]Mavi A, Lakhani P, Zhuang H, et al. Fluorodeoxyglucose-PET in characterizing solitary pulmonary nodules, assessing pleural diseases, and the initial staging, restaging, therapy planning, and monitoring response of lung cancer. Radiol Clin North Am JT - Radiologic clinics of North America, 2005, 43: 1-21.
    [38]Albes JM, Dohmen BM, Schott U, et al. Value of positron emission tomography for lung cancer staging. Eur J Surg Oncol JT-European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology, 2002, 28: 55-62.
    
    [39]Vansteenkiste JF, Stroobants SS. PET scan in lung cancer: current recommendations and innovation. J Thorac Oncol JT- Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2006, 1: 71-73.
    
    [40] Gould MK, Maclean CC, Kuschner WG, et al. Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. JAMA JT-JAMA :the journal of the American Medical Association, 2001, 285: 914-924.
    [41] Marom EM, Sarvis S, Herndon JE 2nd, et al. T1 lung cancers: sensitivity of diagnosis with fluorodeoxyglucose PET. Radiology JT - Radiology, 2002, 223: 453-459.
    [42] Pitman AG, Hicks RJ, Kalff V, et al. Positron emission tomography in pulmonary masses where tissue diagnosis is unhelpful or not possible. Med J Aust JT - The Medical journal of Australia, 2001, 175: 303-307.
    [43] Shim SS, Lee KS, Kim BT, et al. Non-small cell lung cancer: prospective comparison of integrated FDG PET/CT and CT alone for preoperative staging. Radiology JT - Radiology, 2005, 236: 1011-1019.
    [44] Weng E, Tran L, Rege S, et al. Accuracy and clinical impact of mediastinal lymph node staging with FDG-PET imaging in potentially resectable lung cancer. Am J Clin Oncol, 2000, 23: 47-52.
    [45]Holty JE, Kuschner WG, Gould MK. Accuracy of transbronchial needle aspiration for mediastinal staging of non-small cell lung cancer: a meta-analysis. Thorax JT - Thorax, 2005, 60: 949-955.
    [46]Nguyen BD, Fletcher GP,Patel AC. PET/CT imaging of conus medullaris metastasis from lung cancer. Clin Nucl Med JT- Clinical nuclear medicine, 2005, 30: 253-256.
    [47]Stokkel MP, Draisma A,Pauwels EK. Positron emission tomography with 2-[18F]-fluoro-2-deoxy-D-glucose in oncology. Part IIIb: Therapy response monitoring in colorectal and lung tumours, head and neck cancer, hepatocellular carcinoma and sarcoma. J Cancer Res Clin Oncol, 2001,127: 278-285.
    [48] Downey RJ, Akhurst T, Gonen M, et al. Preoperative F-18 fluorodeoxyglucose-positron emission tomography maximal standardized uptake value predicts survival after lung cancer resection. J Clin Oncol, 2004, 22: 3255-3260.
    [49]Zimny M, Kaiser HJ, Wildberger J, et al. Analysis of FDG uptake with hybrid PET using standardised uptake values. Eur J Nucl Med, 2001, 28: 586-592.
    [50]Luker GD, Sharma V, Pica CM, et al. Molecular imaging of protein-protein interactions: controlled expression of p53 and large T-antigen fusion proteins in vivo.Cancer Res JT - Cancer research,2003,63:1780-1788.
    [51]Higashi K,Ueda Y,Ikeda R,et al.P-glycoprotein expression is associated with FDG uptake and cell differentiation in patients with untreated lung cancer.Nucl Med Commun JT - Nuclear medicine communications,2004,25:19-27.
    [52]陈意生,史景泉.肿瘤分子细胞生物学[M].北京:人民军医出版社,2004:15-20.
    [53]Higashi K,Ueda Y,Yagishita M,et al.FDG PET measurement of the proliferative potential of non-small cell lung cancer.J Nucl Med JT - Journal of nuclear medicine:official publication,Society of Nuclear Medicine,2000,41:85-92.
    [54]Smith TA,Titley J.Deoxyglucose uptake by a head and neck squamous carcinoma:influence of changes in proliferative fraction.Int J Radiat Oncol Biol Phys,2000,47:219-223.
    [55]Buck AC,Schirrmeister HH,Guhlmann CA,et al.Ki-67 immunostaining in pancreatic cancer and chronic active pancreatitis:does in vivo FDG uptake correlate with proliferative activity?.J Nucl Med,2001,42:721-725.
    [56]Pedersen MW,Holm S,Lund EL,et al.Coregulation of glucose uptake and vascular endothelial growth factor(VEGF)in two small-cell lung cancer(SCLC)sublines in vivo and in vitro.Neoplasia JT-Neoplasia(New York,N.Y.),2001,3:80-87.
    [57]董春花,李福琴,原丹丹等.GLUT1、VEGF在上皮性卵巢癌中的表达和意义[J].哈尔滨医科大学学报,2006,10:379-381.
    [58]张苜.VEGF受体与肿瘤的关系[J].重庆医学,2006,35(3):267-270.
    [59]高峨嵋,徐建明.VEGF靶向药Avastin治疗实体瘤的研究进展[J].中国肿瘤临床与康复,2006,5:95-97.
    [60]Boivin D,Gendron S,Beaulieu E,et al.The antiangiogenic agent Neovastat (AE-941)induces endothelial cell apoptosis.Mol Cancer Ther,2002,1:795-802.
    [61]何立丽,苏航,张伟京等.血管内皮细胞生长因子与抗肿瘤转移治疗的研究[J].国外医学:药学分册,2006,33(3):165-168.
    [62]崔正军,岑瑛.抑制VEGF在肿瘤治疗中的作用[J].华西医学,2005,1:177-178.
    [63]Li S,Peck-Radosavljevic M,Kienast O,et al.Iodine-123-vascular endothelial growth factor-165(123I-VEGF165).Biodistribution,safety and radiation dosimetry in patients with pancreatic carcinoma. Q J Nucl Med Mol Imaging, 2004,48:198-206.
    [64]Cardones AR, Banez LL. VEGFinhibitors in cancer therapy. Curr Pharm Des, 2006,12: 387-394.
    [65]Chen X, Park R, Shahinian AH, et al. 18F-labeled RGD peptide: initial evaluation for imaging brain tumor angiogenesis. Nucl Med Biol, 2004, 31: 179-189.
    [66]Abourbeh G, Dissoki S, Jacobson O, et al. Evaluation of radiolabeled ML04, a putative irreversible inhibitor of epidermal growth factor receptor, as a bioprobe for PET imaging of EGFR-overexpressing tumors. Nucl Med Biol JT - Nuclear medicine and biology, 2007, 34: 55-70.