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

Leonie Wyffels, Brian D. Gray, Christy Barber, James M. Woolfenden, Koon Y. Pak, Zhonglin Liu

Research output: Contribution to journalArticle

33 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3425-3433
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume19
Issue number11
DOIs
StatePublished - Jun 1 2011

Keywords

  • Cell death
  • Molecular imaging
  • Tc
  • Zn-DPA

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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