title: Synthesis, characterization and biodistribution of a new hexadentate aminethiol ligand labeled with Tc-99m.
abstract: A new hexadentate aminethiol ligand (TACNS) derived from triazacyclononane was synthesized and characterized for the development of technetium radiopharmaceuticals. The ligand formed a neutral, lipophilic and stable complex with [99mTc]pertechnetate in the presence of tin(II)tartarate as a reducing agent. The biodistribution of [99mTc]TACNS indicates slight uptake in brain (0.23% ID/organ at 5 min) with a washout at 30 min to 0.14% ID/organ. A small uptake in heart (0.48% ID at 5 min) was also observed. The characterization of [99mTc]TACNS complex using single crystal x-ray analysis and mass spectroscopy has shown that an Sn-N3S3 complex was formed in which tin is oxidized from Sn(II) to Sn(IV). Pertechnetate was incorporated into the complex as counter anion. The nature of the species formed with Tc-99 and "no-carrier-added" [99mTc]pertechnetate is different as confirmed by ratio TLC. From these results, it is demonstrated that sometimes it may be difficult to predict the structure of new technetium radiopharmaceuticals, especially when stannous ion is used as a reducing agent. Moreover, the nature of the chemical species may not be the same at millimolar and at nanomolar levels.
authors.affiliation: George Washington University Medical Center, Radiopharmaceutical Chemistry Section, DC 20037.
authors.forename: C S
authors.initials: CS
authors.lastname: John
authors.forename: E O
authors.initials: EO
authors.lastname: Schlemper
authors.forename: P
authors.initials: P
authors.lastname: Hosain
authors.forename: C H
authors.initials: CH
authors.lastname: Paik
authors.forename: R C
authors.initials: RC
authors.lastname: Reba
mesh_terms: D000818:Animals; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D007553:Isotope Labeling / Q000379:methods; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D013670:Sodium Pertechnetate Tc 99m / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D013667:Technetium / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D006571:Heterocyclic Compounds; D008024:Ligands; C075711:N,N',N''-tris(2-methyl-(2-mercaptopropyl))-1,4,7-triazacyclononane-pertechnetate; D015609:Organotechnetium Compounds; D013438:Sulfhydryl Compounds; C075712:1,4,7-triazacyclononane; D013667:Technetium; D013670:Sodium Pertechnetate Tc 99m