title: Synthesis and biological evaluation of gallium polyaminothiols (PAT).
abstract: Two polyaminothiol ligands, one hexadentate, N,N',N"-tris[2-methyl(2-propanethiol)]-1,4,7-triazacyclononane (TACN), and another potentially heptadentate, tris[2-methyl(2-propanethiol)]aminoethylamine (TMAE), were synthesized and characterized using spectroscopic and analytical methods. Both ligands were labeled with gallium-67 at pH 3.0-3.5 in high yields. The resulting gallium chelates were lipophilic. The biodistribution studies for both the chelates showed hepatic uptake and biliary clearance. The total % ID activity for [67Ga]TACN in liver and intestine at 5 min was 33.86 increasing gradually to 61.4% at 30 min. The chelates were in vivo stable to plasma-transferrin transchelation as confirmed by scintigraphic images obtained by [67Ga]TACN in rats and by plasma incubation of the chelates. These results indicate that Ga-TACN is a potentially useful tracer for hepatobiliary imaging using PET. No brain uptake was found.
authors.affiliation: Radiopharmaceutical Chemistry Section, George Washington University Medical Center, Washington, DC 20037.
authors.forename: C S
authors.initials: CS
authors.lastname: John
authors.forename: S
authors.initials: S
authors.lastname: Kinuya
authors.forename: G
authors.initials: G
authors.lastname: Minear
authors.forename: R K
authors.initials: RK
authors.lastname: Keast
authors.forename: C H
authors.initials: CH
authors.lastname: Paik
mesh_terms: D000818:Animals; D005029:Ethylenediamines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D005710:Gallium Radioisotopes / Q000493:pharmacokinetics*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011877:Radionuclide Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D005029:Ethylenediamines; D005710:Gallium Radioisotopes; D006571:Heterocyclic Compounds; D013438:Sulfhydryl Compounds; C080232:N,N',N''-tris(2-methyl-(2-propanethiol))-1,4,7-triazacyclononane; C080233:tris(2-methyl-(2-propanethiol))aminoethylamine