title: Preparation and characterization of technetium complexes with Schiff base and phosphine coordination. 1. Complexes of technetium-99g and -99m with substituted acac2en and trialkyl phosphines (where acac2en = N,N'-ethylenebis[acetylacetone iminato]).
abstract: A series of 23 technetium(III) complexes of the type [TcL(PR3)2]+, where L represents a tetradentate Schiff base ligand in the equatorial plane and PR3 represents the axial phosphine ligands, are reported. Full ligand syntheses and characterizations are included. The technetium complexes were prepared with 99mTc to study the organ distribution in guinea pigs at 5 and 60 min postinjection. Four prototypical complexes of the series were also prepared with either 99gTc or 99gTc/99mTc (designated as carrier-added) to allow macroscopic characterization. Equivalence of the 99gTc and 99mTc complexes was demonstrated by dual detection high performance liquid chromatography (HPLC) techniques. The development of a one-step preparation from the standard two-step method is discussed for some complexes. Biodistribution data are related to structure and lipophilicity. None of the complexes in the series exhibited a tendency for in vivo reduction. Myocardial uptake was favorable for a number of complexes. The optimal agent from this series for further imaging development was chosen based on myocardial uptake, rapid blood and liver clearance, and ability to be formulated as a one-step kit.
authors.affiliation: Mallinckrodt Medical Inc., St. Louis, Missouri 63134-0840, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Marmion
authors.forename: S R
authors.initials: SR
authors.lastname: Woulfe
authors.forename: W L
authors.initials: WL
authors.lastname: Neumann
authors.forename: D L
authors.initials: DL
authors.lastname: Nosco
authors.forename: E
authors.initials: E
authors.lastname: Deutsch
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers / Q000737:chemistry; D005663:Furans / Q000737:chemistry / Q000493:pharmacokinetics; D006168:Guinea Pigs; D008024:Ligands; D008297:Male; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D010422:Pentanones / Q000138:chemical synthesis / Q000493:pharmacokinetics; D010720:Phosphines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D012545:Schiff Bases / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship; D013667:Technetium / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D005663:Furans; D008024:Ligands; D015609:Organotechnetium Compounds; D010422:Pentanones; D010720:Phosphines; D019275:Radiopharmaceuticals; D012545:Schiff Bases; C078496:technetium Tc 99m Q12; D013667:Technetium