title: Novel99mTc(III)-azide complexes [99mTc(N3)(CDO)(CDOH)2B-R] (CDOH2=cyclohexanedione dioxime) as potential radiotracers for heart imaging.
abstract: BACKGROUND
  In this study, novel99mTc(III)-azide complexes [99mTc(N3)(CDO)(CDOH)2B-R] (99mTc-ISboroxime-N3: R=IS;99mTc-MPboroxime-N3: R=MP;99mTc-PAboroxime-N3: R=PA;99mTc-PYboroxime-N3: R=PY; and99mTc-Uboroxime-N3: R=5U) were evaluated as heart imaging agents.
  
  
  METHODS
  Complexes [99mTc(N3)(CDO)(CDOH)2B-R] (R=IS, MP, PA, PY and 5U) were prepared by ligand exchange between NaN3and [99mTcCl(CDO)(CDOH)2B-R]. Biodistribution and imaging studies were carried out in Sprague-Dawley rats. Image quantification was performed to compare their initial heart uptake and myocardial retention.
  
  
  RESULTS
  99mTc-ISboroxime-N3,99mTc-PYboroxime-N3and99mTc-Uboroxime-N3were prepared with high RCP (93-98%) while the RCP of99mTc-MPboroxime-N3and99mTc-PAboroxime-N3was 80-85%. The myocardial retention curves of99mTc-ISboroxime-N3,99mTc-PYboroxime-N3and99mTc-Uboroxime-N3were best fitted to the bi-exponential decay function. The half-time of the fast component was 1.6±0.4min for99mTc-ISboroxime-N3, 0.7±0.1min for99mTc-PYboroxime-N3and 0.9±0.4min for99mTc-Uboroxime-N3. The 2-min heart uptake from biodistribution studies followed the ranking order of99mTc-ISboroxime-N3(3.60±0.68%ID/g)>99mTc-PYboroxime-N3(2.35±0.37%ID/g)≫99mTc-Uboroxime-N3(1.29±0.06%ID/g).99mTc-ISboroxime-N3had the highest 2-min heart uptake among99mTc radiotracers revaluated in SD rats. High quality SPECT images were obtained with the right and left ventricular walls being clearly delineated. The best image acquisition window was 0-5min for99mTc-ISboroxime-N3.
  
  
  CONCLUSIONS
  Both azide coligand and boronate caps had significant impact on the heart uptake and myocardial retention of complexes [99mTc(N3)(CDO)(CDOH)2B-R]. Among the radiotracers evaluated in SD rats,99mTc-ISboroxime-N3has the highest initial heart uptake with the heart retention comparable to that of99mTc-Teboroxime.99mTc-ISboroxime-N3is a promising alternative to99mTc-Teboroxime for SPECT MPI.
authors.affiliation: Department of Radiation Medicine and Protection, Medical College, Soochow University, China; School of Health Sciences, Purdue University, IN, 47907, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Nuclear Medicine, China-Japan Friendship Hospital, Beijing, 100037, China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: School of Health Sciences, Purdue University, IN, 47907, USA; Department of Chemistry, Faculty of Arts and Science, Celal Bayar University, 45040, Yunusemre/Manisa, Turkey.
authors.forename: Ugur
authors.initials: U
authors.lastname: Avcibasi
authors.affiliation: School of Health Sciences, Purdue University, IN, 47907, USA. Electronic address: liu100@purdue.edu.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
mesh_terms: D000818:Animals; D006321:Heart / Q000000981:diagnostic imaging*; D007091:Image Processing, Computer-Assisted; D009206:Myocardium / Q000378:metabolism; D015609:Organotechnetium Compounds / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D010091:Oximes / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D011849:Radioactive Tracers; D011854:Radiochemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D015609:Organotechnetium Compounds; D010091:Oximes; D011849:Radioactive Tracers
keywords: (99m)Tc radiotracers; (99m)Tc-Teboroxime derivatives; heart imaging