title: Synthesis and evaluation of cis-1-[4-(hydroxymethyl)-2-cyclopenten-1-yl]-5-[(124)I]iodouracil: a new potential PET imaging agent for HSV1-tk expression.
abstract: In our pursuit to find an appropriate reporter probe for herpes simplex virus type-1 thymidine kinase (HSV1-tk), a carbocyclic nucleoside analogue, cis-1-[4-(hydroxymethyl)-2-cyclopenten-1-yl]-5-[124I]iodouracil, has been efficiently synthesized. A Pd(0)-catalyzed coupling reaction together with organotin and exchange reactions for radiolabeling gave more than 80% radiochemical yield with greater than 95% radiochemical purity and 1.15 GBq/mumol specific activity. Biological data reveal that the analogue is stable in vitro, less toxic than ganciclovir (GCV), and selective to HSV1-tk-expressed cells based on micro positron emission tomography (microPET) image analyses. Thus, this new carbocyclic nucleoside, referred to in this paper as carbocyclic 2',3'-didehydro-2',3'-dideoxy-5-iodouridine (carbocyclic d4IU) is a potential imaging probe for HSV1-tk.
authors.affiliation: Hanyang University, Department of Chemistry and Applied Chemistry, Ansan, Sangrok-Gu, Sa-3-Dong 1271, Kyunggi-Do 426-791, Korea.
authors.forename: Hyunseok
authors.initials: H
authors.lastname: Ahn
authors.forename: Tae Hyun
authors.initials: TH
authors.lastname: Choi
authors.forename: Kathlia
authors.initials: K
authors.lastname: De Castro
authors.forename: Kyo Chul
authors.initials: KC
authors.lastname: Lee
authors.forename: Byoungsoo
authors.initials: B
authors.lastname: Kim
authors.forename: Byung Seok
authors.initials: BS
authors.lastname: Moon
authors.forename: Su Hee
authors.initials: SH
authors.lastname: Hong
authors.forename: Jong Chan
authors.initials: JC
authors.lastname: Lee
authors.forename: Kwon Soo
authors.initials: KS
authors.lastname: Chun
authors.forename: Gi Jeong
authors.initials: GJ
authors.lastname: Cheon
authors.forename: Sang Moo
authors.initials: SM
authors.lastname: Lim
authors.forename: Gwang Il
authors.initials: GI
authors.lastname: An
authors.forename: Hakjune
authors.initials: H
authors.lastname: Rhee
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D018259:Herpesvirus 1, Human / Q000201:enzymology*; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D051379:Mice; D008819:Mice, Nude; D008862:Microsomes, Liver / Q000378:metabolism; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000633:toxicity; D044967:Serum; D013937:Thymidine Kinase / Q000096:biosynthesis*; D014018:Tissue Distribution; D014529:Uridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000633:toxicity
chemical_list: C526814:1-(4-(hydroxymethyl)-2-cyclopenten-1-yl)-5-iodouracil; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D013937:Thymidine Kinase; D014529:Uridine