title: Effect of co-ligands on chemical and biological properties of (99m)Tc(III) complexes [(99m)Tc(L)(CDO)(CDOH)2BMe] (L=Cl, F, SCN and N3; CDOH2=cyclohexanedione dioxime).
abstract: BACKGROUND
  (99m)Tc-Teboroxime ([(99m)TcCl(CDO)(CDOH)2BMe]) is a member of the BATO (boronic acid adducts of technetium dioximes) class of (99m)Tc(III) complexes. This study sought to explore the impact of co-ligands on solution stability, heart uptake and myocardial retention of [(99m)Tc(L)(CDO)(CDOH)2BMe] ((99m)Tc-Teboroxime: L=Cl; (99m)Tc-Teboroxime(F): L=F; (99m)Tc-Teboroxime(SCN): L=SCN; and (99m)Tc-Teboroxime(N3): L=N3).
  
  
  METHODS
  Radiotracers (99m)Tc-Teboroxime(L) (L=F, SCN and N3) were prepared by reacting (99m)Tc-Teboroxime with NaF, NaSCN and NaN3, respectively. Biodistribution and imaging studies were carried out in Sprague-Dawley rats. Image quantification was performed to compare their heart retention and liver clearance kinetics.
  
  
  RESULTS
  Complexes (99m)Tc-Teboroxime(L) (L=F, SCN and N3) were prepared in high yield with high radiochemical purity. All new radiotracers were stable for >6h in the kit matrix. In its HPLC chromatogram, (99m)Tc-Teboroxime showed one peak at ~15.5 min, which was shorter than that of (99m)Tc-Teboroxime(F) (~16.4 min). There were two peaks for (99m)Tc-Teboroxime(SCN) at 16.5 and 18.3 min. (99m)Tc-Teboroxime(N3) appeared as a single peak at 18.4 min. Their heart retention and liver clearance curves were best fitted to the bi-exponential decay function. The half-times of fast/slow components were 1.6±0.4/60.7±8.9 min for (99m)Tc-Teboroxime, 0.8±0.2/101.7±20.7 min for (99m)Tc-Teboroxime(F), 1.2±0.3/84.8±16.6 min for (99m)Tc-Teboroxime(SCN), and 2.9±0.9/51.6±5.0 min for (99m)Tc-Teboroxime(N3). The 2-min heart uptake followed the order of (99m)Tc-Teboroxime (3.00±0.37%ID/g)>(99m)Tc-Teboroxime(N3) (2.66±0.01 %ID/g)≈(99m)Tc-Sestamibi (2.55±0.46 %ID/g)>(99m)TcN-MPO (2.38±0.15 %ID/g). (99m)Tc-Teboroxime remains the best in first-pass extraction. The best image acquisition window is 0-5 min for (99m)Tc-Teboroximine and 0-15 min for (99m)Tc-Teboroximine(N3).
  
  
  CONCLUSIONS
  Co-ligands had significant impact on the heart uptake and myocardial retention of complexes [(99m)Tc(L)(CDO)(CDOH)2BMe] (L=Cl, F, SCN and N3). Future studies should be directed towards minimizing the liver uptake and radioactivity accumulation in the blood vessels while maintaining their high heart uptake.
authors.affiliation: School of Health Sciences, Purdue University, IN 47907, USA; Department of Nuclear Medicine, China-Japan Friendship Hospital, Beijing, 100029, China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: School of Health Sciences, Purdue University, IN 47907, USA.
authors.forename: Shundong
authors.initials: S
authors.lastname: Ji
authors.affiliation: School of Health Sciences, Purdue University, IN 47907, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Tomaselli
authors.affiliation: School of Health Sciences, Purdue University, IN 47907, USA.
authors.forename: Carley
authors.initials: C
authors.lastname: Ernest
authors.affiliation: School of Health Sciences, Purdue University, IN 47907, USA.
authors.forename: Tom
authors.initials: T
authors.lastname: Freiji
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; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging*; D008099:Liver / Q000000981:diagnostic imaging; D008168:Lung / Q000000981:diagnostic imaging; D008297:Male; D015609:Organotechnetium Compounds; D010091:Oximes / Q000737:chemistry; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D015609:Organotechnetium Compounds; D010091:Oximes; D019275:Radiopharmaceuticals
keywords: (99m)Tc radiotracers; (99m)Tc-Teboroxime derivatives; Heart imaging