title: Synthesis and preliminary evaluation of radiolabeled bis(zinc(II)-dipicolylamine) coordination complexes as cell death imaging agents.
abstract: The aim of this study was the development of (⁹⁹m)Tc labeled bis(zinc(II)-dipicolylamine) (Zn²⁺-DPA) coordination complexes, and the in vivo evaluation of their usefulness as radiotracers for the detection of cell death. DPA ligand 1 was labeled with (⁹⁹m)Tc via the (⁹⁹m)Tc-tricarbonyl core ([(⁹⁹m)Tc(CO)₃-1]³⁺) or via HYNIC ((⁹⁹m)Tc-HYNIC-1) in good radiochemical yields. Highest in vitro stabilities were demonstrated for [(⁹⁹m)Tc(CO)₃-1]³⁺. A mouse model of hepatic apoptosis (anti-Fas mAb) was used to demonstrate binding to apoptotic cells. (⁹⁹m)Tc-HYNIC-1 showed the best targeting of apoptotic hepatic tissue with a 2.2 times higher liver uptake in anti-Fas treated mice as compared to healthy animals. A rat model of ischemia-reperfusion injury was used to further explore the ability of the (⁹⁹m)Tc-labeled Zn²⁺-DPA coordination complexes to target cell death. Selective accumulation could be detected for both tracers in the area at risk, correlating with histological proof of cell death. Area at risk to normal tissue uptake ratios were 3.82 for [(⁹⁹m)Tc(CO)₃-1]³⁺ and 5.45 for (⁹⁹m)Tc-HYNIC-1.
authors.affiliation: Department of Radiology, University of Arizona, Tucson, AZ, USA.
authors.forename: Leonie
authors.initials: L
authors.lastname: Wyffels
authors.forename: Brian D
authors.initials: BD
authors.lastname: Gray
authors.forename: Christy
authors.initials: C
authors.lastname: Barber
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Moore
authors.forename: James M
authors.initials: JM
authors.lastname: Woolfenden
authors.forename: Koon Y
authors.initials: KY
authors.lastname: Pak
authors.forename: Zhonglin
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D008099:Liver / Q000000981:diagnostic imaging; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011725:Pyridines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000000981:diagnostic imaging / Q000473:pathology; D013667:Technetium / Q000737:chemistry; D014018:Tissue Distribution; D015032:Zinc / Q000737:chemistry*
chemical_list: D056831:Coordination Complexes; D015609:Organotechnetium Compounds; D011725:Pyridines; D019275:Radiopharmaceuticals; D013667:Technetium; D015032:Zinc