title: Study of [18F]FLT and [123I]IaraU for cellular imaging in HSV1 tk-transfected murine fibrosarcoma cells: evaluation of the tracer uptake using 5-fluoro, 5-iodo and 5-iodovinyl arabinosyl uridines as competitive probes.
abstract: As one of the most intensively studied probes for imaging of the cellular proliferation, [(18)F]FLT was investigated whether the targeting specificity of thymidine kinase 1 (TK1) dependency could be enhanced through a synergistic effect mediated by herpes simplex type 1 virus (HSV1) tk gene in terms of the TK1 or TK2 expression. 5-[(123)I]Iodo arabinosyl uridine ([(123)I]IaraU) was prepared in a radiochemical yield of 8% and specific activity of 21 GBq/μmol, respectively. Inhibition of the cellular uptake of these two tracers was compared by using the arabinosyl uridine analogs such as 5-iodo, 5-fluoro and 5-(E)-iodovinyl arabinosyl uridine along with 2'-fluoro-5-iodo arabinosyl uridine (FIAU). Due to potential instability of the iodo group, accumulation index of 1.6 for [(123)I]IaraU by HSV1-TK vs. control cells could virtually be achieved at 1.5 h, but dropped to 0.2 compared to 2.0 for [(18)F]FLT at 5 h. The results from competitive inhibition by these nucleosides against the accumulation of [(18)F]FLT implied that FLT exerted a mixed TK1- and TK2-dependent inhibition with HSV1-tk gene transfection because of the shifting of thymidine kinase status. Taken together, the combination of [(18)F]FLT and HSV1-TK provides a synergistic imaging potency.
authors: Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, Hsinchu 300, Taiwan.
authors: Ho-Lien
authors: HL
authors: Huang
authors: Li-Wu
authors: LW
authors: Chiang
authors: Jia-Rong
authors: JR
authors: Chen
authors: Wen K
authors: WK
authors: Yang
authors: Kee-Ching
authors: KC
authors: Jeng
authors: Jenn-Tzong
authors: JT
authors: Chen
authors: Ting-Shien
authors: TS
authors: Duh
authors: Wuu-Jyh
authors: WJ
authors: Lin
authors: Shiou-Shiow
authors: SS
authors: Farn
authors: Chi-Shiun
authors: CS
authors: Chiang
authors: Chia-Wen
authors: CW
authors: Huang
authors: Kun-I
authors: KI
authors: Lin
authors: Chung-Shan
authors: CS
authors: Yu
mesh_terms: D000818:Animals; D048708:Cell Growth Processes; D045744:Cell Line, Tumor; D015224:Dideoxynucleosides / Q000737:chemistry / Q000493:pharmacokinetics*; D005354:Fibrosarcoma / Q000000981:diagnostic imaging* / Q000201:enzymology / Q000235:genetics; D018259:Herpesvirus 1, Human / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D007457:Iodine Radioisotopes / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013937:Thymidine Kinase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014529:Uridine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: C525774:5-fluoro arabinosyl uridine; C525775:5-iodo arabinosyl uridine; C525776:5-iodovinyl arabinosyl uridine; D015224:Dideoxynucleosides; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; C105339:thymidine kinase 2; D013937:Thymidine Kinase; C092717:thymidine kinase 1; C002854:alovudine; D014529:Uridine