Synthesis and preliminary evaluation of radiolabeled bis(zinc(II)- dipicolylamine) coordination complexes as cell death imaging agents

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.