title: In vivo evaluation of the uptake of [(123)I]FIAU, [(123)I]IVFRU and [(123)I]IVFAU by normal mouse brain: potential for noninvasive assessment of HSV-1 thymidine kinase gene expression in gliomas.
abstract: Radioiodinated 5-iodo-1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)uracil (F *IAU) is most commonly used for noninvasive assessment of herpes simplex virus type 1 thymidine kinase (HSV-1-tk) gene expression. However, it does not permeate the intact blood-brain barrier (BBB) because of its moderate lipophilicity. In this work, three iodo-nucleosides, FIAU, IVFRU, and IVFAU, were radiolabeled with iodine-123 and tested for permeation of the BBB in mice and for potential measurement of HSV-1-tk gene expression in gliomas. The results demonstrate that brain uptake and retention of these nucleosides is not directly related to their lipophilicity. The low brain uptake of IVFAU, in conjunction with its higher and constant brain/blood ratio, may reflect greater stability against hydrolysis of the N-glycosidic bond. In vivo PET evaluations of [(124)I]IVFRU and [(124)I]IVFAU in tumor-bearing mice are warranted.
authors.affiliation: Department of neurology, University of Cologne, Cologne, Germany. Lisa.Li@nf.mpg.de
authors.forename: H-F
authors.initials: HF
authors.lastname: Li
authors.forename: A
authors.initials: A
authors.lastname: Winkeler
authors.forename: S
authors.initials: S
authors.lastname: Moharram
authors.forename: E E
authors.initials: EE
authors.lastname: Knaus
authors.forename: K
authors.initials: K
authors.lastname: Dittmar
authors.forename: M
authors.initials: M
authors.lastname: Stöckle
authors.forename: W D
authors.initials: WD
authors.lastname: Heiss
authors.forename: L I
authors.initials: LI
authors.lastname: Wiebe
authors.forename: A H
authors.initials: AH
authors.lastname: Jacobs
authors.forename: A J
authors.initials: AJ
authors.lastname: Jacob
mesh_terms: D000818:Animals; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000821:virology; D001932:Brain Neoplasms / Q000201:enzymology / Q000821:virology; D005467:Floxuridine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D015870:Gene Expression; D005910:Glioma / Q000201:enzymology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000201:enzymology; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008819:Mice, Nude; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution; D014529:Uridine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: C527997:5-(2-iodovinyl)-2'-fluoro-2'-deoxyarabinouridine; D007457:Iodine Radioisotopes; D005467:Floxuridine; C060868:5-(2-iodovinyl)-1-(2'-fluoro-2'-deoxyuridine); D001086:Arabinofuranosyluracil; C043457:fialuridine; D013937:Thymidine Kinase; D014529:Uridine