title: Inter-heterogeneity and intra-heterogeneity of αvβ3in non-small cell lung cancer and small cell lung cancer patients as revealed by68Ga-RGD2PET imaging.
abstract: OBJECTIVE
  Integrin αvβ3is the therapeutic target of the anti-angiogenic drug cilengitide. The objective of this study was to compare αvβ3levels in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients, by using the positron emission tomography (PET) tracer68Ga-labeled dimerized-RGD (68Ga-RGD2).
  
  
  METHODS
  Thirty-one patients with pathologically confirmed lung cancer were enrolled (21 were NSCLC and 10 were SCLC). PET/CT images were acquired using68Ga-RGD2.18F-FDG PET/CT images were also acquired on the consecutive day as reference. The standard uptake values (SUV) and the tumor/nontarget (T/NT) values were quantitatively compared. Expression of the angiogenesis marker αvβ3in NSCLC and SCLC lesions was analyzed by immunohistochemistry.
  
  
  RESULTS
  The18F-FDG SUVmax and the SUVmean were not significantly different between NSCLC and SCLC patients. The68Ga-RGD2uptake of SCLC patients was at background levels in both SUV and T/NT measurements and was significantly lower than that of NSCLC patients. The range value of68Ga-RGD2SUVmean was 4.5 in the NSCLC group and 2.2 in the SCLC group, while the variation coefficient was 36.2% and 39.3% in NSCLC and SCLC primary lesions, respectively. Heterogeneity between primary lesions and putative distant metastases was also observed in some NSCLC cases. Immunostaining showed that αvβ3integrin was expressed in the cells and neovasculature of NSCLC lesions, while SCLC samples had negative expression.
  
  
  CONCLUSIONS
  The uptake of68Ga-RGD2in SCLC patients is significantly lower than that in NSCLC patients, indicating a lower αvβ3target level for cilengitide in SCLC. Apparent intra-tumor heterogeneities of αvβ3also exist in both NSCLC and SCLC. Such inter- and intra-heterogeneity of αvβ3may potentially improve current applications of αvβ3-targeted therapy and diagnostic imaging in lung cancer.
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, No.127 West Changle Road, Xi'an, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Kang
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, No.127 West Changle Road, Xi'an, People's Republic of China.|Department of Pathology, Xijing Hospital, Fourth Military Medical University, No. 127 West Changle Road, Xi'an, People's Republic of China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, No.127 West Changle Road, Xi'an, People's Republic of China.
authors.forename: Guoquan
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, No.127 West Changle Road, Xi'an, People's Republic of China.
authors.forename: Shengjun
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, No.127 West Changle Road, Xi'an, People's Republic of China.
authors.forename: Daliang
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, No.127 West Changle Road, Xi'an, People's Republic of China.
authors.forename: Mingru
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, No.127 West Changle Road, Xi'an, People's Republic of China.
authors.forename: Mingxuan
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, No.127 West Changle Road, Xi'an, People's Republic of China. yangwd1971@163.com.
authors.forename: Weidong
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, No.127 West Changle Road, Xi'an, People's Republic of China. wangjing@fmmu.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D001692:Biological Transport; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000378:metabolism*; D019281:Dimerization; D005260:Female; D005710:Gallium Radioisotopes; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000737:chemistry*; D049268:Positron-Emission Tomography; D055752:Small Cell Lung Carcinoma / Q000000981:diagnostic imaging / Q000378:metabolism*
chemical_list: D005710:Gallium Radioisotopes; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; C000615430:Gallium-68
keywords: 68Ga-labeled dimerized-RGD; Cilengitide; Integrin αvβ3; Non-small cell lung cancer; Small cell lung cancer