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).

Introduction: (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).
Conclusion: 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.
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