Novel (99m)Tc(III)-azide complexes [(99m)Tc(N3)(CDO)(CDOH)2B-R] (CDOH2=cyclohexanedione dioxime) as potential radiotracers for heart imaging.

INTRODUCTION: In this study, novel (99m)Tc(III)-azide complexes [(99m)Tc(N3)(CDO)(CDOH)2B-R] ((99m)Tc-ISboroxime-N3: R=IS; (99m)Tc-MPboroxime-N3: R=MP; (99m)Tc-PAboroxime-N3: R=PA; (99m)Tc-PYboroxime-N3: R=PY; and (99m)Tc-Uboroxime-N3: R=5U) were evaluated as heart imaging agents.

METHODS: Complexes [(99m)Tc(N3)(CDO)(CDOH)2B-R] (R=IS, MP, PA, PY and 5U) were prepared by ligand exchange between NaN3 and [(99m)TcCl(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: (99m)Tc-ISboroxime-N3, (99m)Tc-PYboroxime-N3 and (99m)Tc-Uboroxime-N3 were prepared with high RCP (93-98%) while the RCP of (99m)Tc-MPboroxime-N3 and (99m)Tc-PAboroxime-N3 was 80-85%. The myocardial retention curves of (99m)Tc-ISboroxime-N3, (99m)Tc-PYboroxime-N3 and (99m)Tc-Uboroxime-N3 were best fitted to the bi-exponential decay function. The half-time of the fast component was 1.6±0.4min for (99m)Tc-ISboroxime-N3, 0.7±0.1min for (99m)Tc-PYboroxime-N3 and 0.9±0.4min for (99m)Tc-Uboroxime-N3. The 2-min heart uptake from biodistribution studies followed the ranking order of (99m)Tc-ISboroxime-N3 (3.60±0.68%ID/g)>(99m)Tc-PYboroxime-N3 (2.35±0.37%ID/g)≫(99m)Tc-Uboroxime-N3 (1.29±0.06%ID/g). (99m)Tc-ISboroxime-N3 had the highest 2-min heart uptake among (99m)Tc 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 for (99m)Tc-ISboroxime-N3.

CONCLUSION: Both azide coligand and boronate caps had significant impact on the heart uptake and myocardial retention of complexes [(99m)Tc(N3)(CDO)(CDOH)2B-R]. Among the radiotracers evaluated in SD rats, (99m)Tc-ISboroxime-N3 has the highest initial heart uptake with the heart retention comparable to that of (99m)Tc-Teboroxime. (99m)Tc-ISboroxime-N3 is a promising alternative to (99m)Tc-Teboroxime for SPECT MPI.