title: 3'-Deoxy-3'-[18F]fluorothymidine positron emission tomography imaging of thymidine kinase 1 activity after 5-fluorouracil treatment in a mouse tumor model.
abstract: OBJECTIVE
  We aimed to investigate whether 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) positron emission tomography (PET) can estimate thymidine kinase 1 (TK1) activity after thymidylate synthase (TS) inhibition by 5-fluorouracil (5-FU) in a mouse tumor model.
  
  
  METHODS
  Nude mice with HT29 tumors were injected with phosphate-buffered saline or 5-FU (16.7 or 50 mg/kg). Twenty-four hours later, 2-hour dynamic images were acquired after injection of [(18)F]FLT. In another group of mice with HT29 cells, static PET images were obtained 110 min after [(18)F]FLT injection.
  
  
  RESULTS
  Kinetic parameters related to [(18)F]FLT retention increased significantly, whereas the de-phosphorylation of [(18)F]FLT monophosphate decreased significantly. The standardized uptake value (SUVmean) of HT29 tumors correlated significantly with the net influx constant and the distribution volume for phosphorylated [(18)F]FLT. There was a significant correlation between the tumor SUVmean and TK1 activity.
  
  
  CONCLUSIONS
  SUVmean at 110-120 min after [(18)F]FLT, can quantitatively evaluate kinetic parameters and TK1 activity after TS inhibition.
authors: Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Republic of Korea. dhmoon@amc.seoul.kr.
authors: Il Ki
authors: IK
authors: Hong
authors: Seog Young
authors: SY
authors: Kim
authors: Jin Hwa
authors: JH
authors: Chung
authors: Seung Jin
authors: SJ
authors: Lee
authors: Seung Jun
authors: SJ
authors: Oh
authors: Sang Ju
authors: SJ
authors: Lee
authors: Jungsu
authors: J
authors: Oh
authors: Jin-Sook
authors: JS
authors: Ryu
authors: Tae Won
authors: TW
authors: Kim
authors: Deog Yoon
authors: DY
authors: Kim
authors: Dae Hyuk
authors: DH
authors: Moon
mesh_terms: D000818:Animals; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000201:enzymology; D015224:Dideoxynucleosides / Q000737:chemistry / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D005472:Fluorouracil / Q000494:pharmacology*; D019073:HT29 Cells; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010766:Phosphorylation; D049268:Positron-Emission Tomography; D013937:Thymidine Kinase / Q000737:chemistry / Q000378:metabolism*; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D015224:Dideoxynucleosides; D013940:Thymidylate Synthase; D013937:Thymidine Kinase; C092717:thymidine kinase 1; C002854:alovudine; D005472:Fluorouracil
keywords: 3’-deoxy-3’-[18F]fluorothymidine; 5-fluorouracil; positron emission tomography; thymidine kinase; thymidylate synthase