title: 5-O-(4-[125 I]Iodobenzyl)-L-ascorbic acid: electrophilic radioiodination and biodistribution in mice.
abstract: As a part of our efforts to develop potential imaging agents for ascorbate bioactivity, 5-O-(4-[(125)I]iodobenzyl)-L-ascorbic acid ([(125)I]1) was prepared through a two-step sequence which involved radioiodo-destannylation of a protected tributylstannyl precursor 6, followed by hydrolysis in acidic methanol of the protecting groups in 61% overall radiochemical yield, with a radiochemical purity of over 98% and a specific activity of more than 15.4 GBq/μmol. Tissue distribution of [(125)I]1 in tumor-bearing mice showed signs of distribution profiles similar to the reported results for 6-deoxy-6-[(18)F]fluoro-L-ascorbic (6-(18)FAsA) acid and 6-deoxy-6-[(131)I]iodo-L-ascorbic acid (6-(131)IAsA) but with notable differences in the adrenal glands, in which considerably lower uptake of radioactivity and rapid clearance with time were observed. Pretreatment of mice with a known inhibitor of ascorbate transport, sulfinpyrazone, did not produce any significant change in the adrenal uptake of radioactivity after injection of [(125)I]1 compared to the control, suggesting that uptake in the adrenal glands is independent of the sodium-dependent vitamin C transporter 2 transport mechanism. Introduction of a bulky substituent at C-5 on AsA, such as an iodobenzyloxy group, may not be suitable for the design of analogs that may still be able to maintain characteristic distribution properties in vivo seen with AsA itself.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, 3–1–1 Maidashi, Higashi-ku, Fukuoka, Japan.
authors.forename: Jintaek
authors.initials: J
authors.lastname: Kim
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kino
authors.forename: Hiroharu
authors.initials: H
authors.lastname: Kato
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Yamamoto
authors.forename: Kohei
authors.initials: K
authors.lastname: Sano
authors.forename: Takahiro
authors.initials: T
authors.lastname: Mukai
authors.forename: Minoru
authors.initials: M
authors.lastname: Maeda
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D005354:Fibrosarcoma / Q000000981:diagnostic imaging; D007457:Iodine Radioisotopes; D051379:Mice; D015394:Molecular Structure; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000737:chemistry* / Q000493:pharmacokinetics*
chemical_list: C572641:5-O-(4-(125 I)iodobenzyl)-L-ascorbic acid; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D001205:Ascorbic Acid