Title
Synthesis and preliminary evaluation of radiolabeled bis(zinc(II)dipicolylamine) coordination complexes as cell death imaging agents Synthesis and preliminary evaluation of radiolabeled bis(zinc(II)dipicolylamine) coordination complexes as cell death imaging agents
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Oxford ,
Subject
Pharmacology. Therapy
Source (journal)
Bioorganic and medicinal chemistry. - Oxford
Volume/pages
19(2011) :11 , p. 3425-3433
ISSN
0968-0896
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Abstract
The aim of this study was the development of 99mTc 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 99mTc via the 99mTc-tricarbonyl core ([99mTc(CO)3-1]3+) or via HYNIC (99mTc-HYNIC-1) in good radiochemical yields. Highest in vitro stabilities were demonstrated for [99mTc(CO)3-1]3+. A mouse model of hepatic apoptosis (anti-Fas mAb) was used to demonstrate binding to apoptotic cells. 99mTc-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 99mTc-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 [99mTc(CO)3-1]3+ and 5.45 for 99mTc-HYNIC-1.
E-info
https://repository.uantwerpen.be/docman/iruaauth/774127/a3a02d235dd.pdf