title: Synthesis and biodistribution of 3'-fluoro-5-[(131)I]iodo-2'-deoxyuridine: a comparative study of [(131)I]FLIdU and [(18)F]FLT.
abstract: The radioiodinated 3'-fluorothymidine (FLT) analogue 3'-fluoro-5-[(131)I]iodo-2'-deoxyuridine ([(131)I]FLIdU) was synthesized, with iodine mimicking the methyl group of pyrimidine. [(131)I]FLIdU was accessible by direct electrophilic iodination using Iodogen as oxidant. Optimized amounts of the oxidant allowed radiochemical yields of about 70% after a reaction time of 10 min in an aqueous buffer medium at 90 degrees C. The uptake of [(131)I]FLIdU in a DoHH2 leukemia xenograft mouse model and in healthy mice revealed moderate FLIdU accumulation, followed by a significant washout of activity in proliferating tissues such as splenic and tumor tissues. In contrast, intraperitoneal coinjection with [(18)F]FLT showed high uptake and high activity retention up to 2 h, in both splenic and tumor tissues. Uptake in stomach tissues and increasing fractions of [(131)I]iodide in urine indicated metabolic instability of [(131)I]FLIdU due to rapid deiodination. Therefore, [(131)I]FLIdU alone does not seem to be a promising compound, neither for diagnostic imaging nor for potential therapeutic applications.
authors: Clinic for Nuclear Medicine, D-89081 Ulm, Germany. andreas.vogg@itm.ag
authors: Andreas T J
authors: AT
authors: Vogg
authors: Andreas K
authors: AK
authors: Buck
authors: Michaela
authors: M
authors: Schmid
authors: Bernd
authors: B
authors: Neumaier
authors: Katrin
authors: K
authors: Wczasek
authors: Boris D
authors: BD
authors: Zlatopolskiy
authors: Sven N
authors: SN
authors: Reske
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D015224:Dideoxynucleosides / Q000737:chemistry / Q000493:pharmacokinetics*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D008223:Lymphoma / Q000000981:diagnostic imaging / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D051379:Mice; D016513:Mice, SCID; D009928:Organ Specificity; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: C521345:3'-fluoro-5-iodo-2'-deoxyuridine; D015224:Dideoxynucleosides; D019275:Radiopharmaceuticals; C002854:alovudine; D003857:Deoxyuridine