title: Stable and lipophilic technetium-99m dithiosemicarbazone complexes with 5-6-5 membered chelate ring structure.
abstract: Modification of the chelate ring structure of technetium-99m (99mTc) dithiosemicarbazone (DTS) chelate was carried out in pursuit of a more stable and lipophilic compound. A new DTS chelating molecule, pentane-2,4-dione bis(N-methylthiosemicarbazone) (PETS), with a 5-6-5 membered chelate ring structure, was synthesized and labeled with 99mTc, PETS generated two 99mTc compounds as major products. Both had much higher stability and lipophilicity than a 5-5-5 membered 99mTc DTS compound, as well as great stability in plasma. Both 99mTc-PETS compounds were rapidly extracted by the brain and heart when injected into mice. Thus, the modified chelate ring structure afforded a preferable characteristics to DTS chelate as for the chelating site for technetium radiopharmaceuticals.
authors.affiliation: Department of Radiopharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Arano
authors.forename: M
authors.initials: M
authors.lastname: Yabuki
authors.forename: T
authors.initials: T
authors.lastname: Yahata
authors.forename: K
authors.initials: K
authors.lastname: Horiuchi
authors.forename: A
authors.initials: A
authors.lastname: Yokoyama
mesh_terms: D000818:Animals; D004355:Drug Stability; D008055:Lipids; D008297:Male; D051379:Mice; D015609:Organotechnetium Compounds / Q000737:chemistry* / Q000493:pharmacokinetics; D012995:Solubility; D013882:Thiosemicarbazones / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D008055:Lipids; D015609:Organotechnetium Compounds; D013882:Thiosemicarbazones; C068197:technetium Tc 99m diacetyl bis(N-methylthiosemicarbazone); C068196:technetium Tc 99m pentane-2,4-dione bis(N-methylthiosemicarbazone)