Effect of co-ligands on chemical and biological properties of 99mTc(III) complexes [99mTc(L)(CDO)(CDOH)2BMe] (L = Cl, F, SCN and N3; CDOH2 = cyclohexanedione dioxime)

Abstract

Introduction99mTc-Teboroxime ([99mTcCl(CDO)(CDOH)2BMe]) is a member of the BATO (boronic acid adducts of technetium dioximes) class of 99mTc(III) complexes. This study sought to explore the impact of co-ligands on solution stability, heart uptake and myocardial retention of [99mTc(L)(CDO)(CDOH)2BMe] (99mTc-Teboroxime: L=Cl; 99mTc-Teboroxime(F): L=F; 99mTc-Teboroxime(SCN): L=SCN; and 99mTc-Teboroxime(N3): L=N3). MethodsRadiotracers 99mTc-Teboroxime(L) (L=F, SCN and N3) were prepared by reacting 99mTc-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. ResultsComplexes 99mTc-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, 99mTc-Teboroxime showed one peak at ~15.5min, which was shorter than that of 99mTc-Teboroxime(F) (~16.4min). There were two peaks for 99mTc-Teboroxime(SCN) at 16.5 and 18.3min. 99mTc-Teboroxime(N3) appeared as a single peak at 18.4min. 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±8.9min for 99mTc-Teboroxime, 0.8±0.2/101.7±20.7min for 99mTc-Teboroxime(F), 1.2±0.3/84.8±16.6min for 99mTc-Teboroxime(SCN), and 2.9±0.9/51.6±5.0min for 99mTc-Teboroxime(N3). The 2-min heart uptake followed the order of 99mTc-Teboroxime (3.00±0.37%ID/g)>99mTc-Teboroxime(N3) (2.66±0.01 %ID/g)≈99mTc-Sestamibi (2.55±0.46 %ID/g)>99mTcN-MPO (2.38±0.15 %ID/g). 99mTc-Teboroxime remains the best in first-pass extraction. The best image acquisition window is 0–5min for 99mTc-Teboroximine and 0–15min for 99mTc-Teboroximine(N3). ConclusionCo-ligands had significant impact on the heart uptake and myocardial retention of complexes [99mTc(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.