title: (99m)Tc-3P-RGD2 micro-single-photon emission computed tomography/computed tomography provides a rational basis for integrin αvβ3-targeted therapy.
abstract: OBJECTIVE
  This study was to demonstrate the utility of (99m)Tc-3P-RGD2 micro-single-photon emission computed tomography/computed tomography (SPECT/CT) for the integrin αvβ3 expression quantification in NCI-H446 and A549 lung cancer xenografts.
  
  
  METHODS
  (99m)Tc-3P-RGD2 was prepared with high radiochemical purity (97%±2%) and showing high in vitro stability. The in vitro affinities of (99m)Tc-3P-RGD2 to NCI-H446 and A549 tumor cells were analyzed with γ-counter, while the in vivo uptakes in NCI-H446 and A549 xenografts were evaluated with micro-SPECT/CT. The region of interest was drawn over the tumor site and contralateral muscle on the SPECT/CT image, and the tumor to nontumor (T/NT) ratio was calculated to estimate αvβ3 expression and tumor uptake. The expressions of integrin αvβ3 in vitro and in vivo were analyzed using a flow cytometer and immunofluorescence.
  
  
  RESULTS
  Micro-SPECT/CT demonstrated focal uptake in the tumors. T/NT ratio in NCI-H446 xenografts was significantly higher compared with the A549 tumor model, as 5.92±0.82 and 3.62±0.91, respectively, with p<0.05. In addition, integrin αvβ3 expression in NCI-H446 cells was significantly higher compared with the A549 cells, which was consistent with the imaging data. A linear relationship was observed between (99m)Tc-3P-RGD2 uptake and αvβ3 expression (R(2)=0.7667, p<0.001).
  
  
  CONCLUSIONS
  (99m)Tc-3P-RGD2 SPECT/CT could be used to quantify integrin αvβ3 expression within tumors, providing a rational basis for integrin αvβ3-targeted cancer therapy.
authors.affiliation: 1 Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University , Nanjing, Jiangsu Province, People's Republic of China .
authors.forename: Tong
authors.initials: T
authors.lastname: Fu
authors.forename: Wei
authors.initials: W
authors.lastname: Qu
authors.forename: Fan
authors.initials: F
authors.lastname: Qiu
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Shao
authors.forename: Wei
authors.initials: W
authors.lastname: Tian
authors.forename: Zichun
authors.initials: Z
authors.lastname: Hua
authors.forename: Yingjian
authors.initials: Y
authors.lastname: Zhang
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000096:biosynthesis*; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D064847:Multimodal Imaging; D009842:Oligopeptides / Q000493:pharmacokinetics; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D055752:Small Cell Lung Carcinoma / Q000000981:diagnostic imaging* / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D014057:Tomography, X-Ray Computed / Q000379:methods; D023041:Xenograft Model Antitumor Assays
chemical_list: D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C047981:arginyl-glycyl-aspartic acid
keywords: 99mTc-3P-RGD2; NSCLC; anti-angiogenesis; integrin αvβ3; quantification