title: Syntheses and preliminary evaluation of [(18) F]AlF-NOTA-G-TMTP1 for PET imaging of high aggressive hepatocellular carcinoma.
abstract: The goal of this study is to evaluate a new (18) F-labeled imaging agent for diagnosing high metastatic (aggressive) hepatocellular carcinoma using positron emission tomography (PET). The new (18) F-labeled imaging agent [(18) F]AlF-NOTA-G-TMTP1 was synthesized and radiolabeled with (18) F using NOTA-AlF chelation method. The tumor-targeting characteristics of [(18) F]AlF-NOTA-G-TMTP1 was assessed in HepG2, SMCC-7721, HCC97L and HCCLM3 xenografts. The total synthesis time was about 20 min with radiochemical yield of 25 ± 6%. The specific activity was about 11.1-14.8 GBq/µmol at the end of synthesis based on the amount of peptide used and the amount of radioactivity trapped on the C18 column. The log P value of [(18) F]AlF-NOTA-G-TMTP1 was -3.166 ± 0.022. [(18) F]AlF-NOTA-G-TMTP1 accumulated in SMCC-7721 and HCCLM3 tumors (high metastatic potential) in vivo and result in tumor/muscle (T/M) ratios of 4.5 ± 0.3 and 4.7 ± 0.2 (n = 4) as measured by PET at 40 min post-injection (p.i.). Meanwhile, the tumor/muscle (T/M) ratios of HepG2 and HCC97L tumors (low metastatic potential) were1.6 ± 0.3 and 1.8 ± 0.4. The tumor uptake of [(18) F]AlF-NOTA-G-TMTP1 could be inhibited 61.9% and 57.6% by unlabeled G-TMTP1 in SMCC-7721 and HCCLM3 xenografts at 40 min p.i., respectively. Furthermore, [(18) F]AlF-NOTA-G-TMTP1 showed pretty low activity in the liver and intestines in all tumor bearing mice, such in vivo distribution pattern would be advantageous for the detection of hepatic carcinoma. Overall, [(18) F]AlF-NOTA-G-TMTP1 may specifically target high metastatic or/and aggressive hepatocellular carcinoma with low background activity and, therefore, holds the potential to be used as an imaging agent for detecting tumor lesions within the liver area. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Nuclear Medicine, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, China.|CMITM, SKLMVMD, School of Public Health, Xiamen University, Xiamen, 361005, China.
authors.forename: Yesen
authors.initials: Y
authors.lastname: Li
authors.affiliation: CMITM, SKLMVMD, School of Public Health, Xiamen University, Xiamen, 361005, China.
authors.forename: Deliang
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital affiliated to Xiamen University, 201 Hubin South Road, Xiamen, 361004, Fujian, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shi
authors.affiliation: CMITM, SKLMVMD, School of Public Health, Xiamen University, Xiamen, 361005, China.
authors.forename: Zhide
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China.
authors.forename: Xinying
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital affiliated to Xiamen University, 201 Hubin South Road, Xiamen, 361004, Fujian, China.
authors.forename: Jian-Lin
authors.initials: JL
authors.lastname: Ren
authors.affiliation: CMITM, SKLMVMD, School of Public Health, Xiamen University, Xiamen, 361005, China.
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Nuclear Medicine, The First Affiliated Hospital of Xiamen University, Xiamen, 361003, China.|CMITM, SKLMVMD, School of Public Health, Xiamen University, Xiamen, 361005, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wu
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging* / Q000473:pathology; D005462:Fluorine Radioisotopes; D056945:Hep G2 Cells; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; D064593:Heterografts; D006801:Humans; D007414:Intestinal Neoplasms / Q000556:secondary; D008113:Liver Neoplasms / Q000000981:diagnostic imaging*; D051379:Mice; D009362:Neoplasm Metastasis / Q000000981:diagnostic imaging; D009842:Oligopeptides; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D005462:Fluorine Radioisotopes; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; D009842:Oligopeptides; D019275:Radiopharmaceuticals; C531959:asparagyl-valyl-valyl-arginyl-glutamine; C048993:1,4,7-triazacyclononane-N,N',N''-triacetic acid
keywords: 18F-AlF chelation; 18F-labeling; G-TMTP1; PET imaging; high metastatic