Novel 99m Tc(III)-azide complexes [ 99m Tc(N 3)(CDO)(CDOH) 2 B-R] (CDOH 2=cyclohexanedione dioxime) as potential radiotracers for heart imaging

Nucl Med Biol. 2016 Nov;43(11):732-741. doi: 10.1016/j.nucmedbio.2016.05.001. Epub 2016 May 9.


Introduction: In this study, novel 99mTc(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; and 99mTc-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 NaN3 and [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-N3 and 99mTc-Uboroxime-N3 were prepared with high RCP (93-98%) while the RCP of 99mTc-MPboroxime-N3 and 99mTc-PAboroxime-N3 was 80-85%. The myocardial retention curves of 99mTc-ISboroxime-N3, 99mTc-PYboroxime-N3 and 99mTc-Uboroxime-N3 were best fitted to the bi-exponential decay function. The half-time of the fast component was 1.6±0.4min for 99mTc-ISboroxime-N3, 0.7±0.1min for 99mTc-PYboroxime-N3 and 0.9±0.4min for 99mTc-Uboroxime-N3. The 2-min heart uptake from biodistribution studies followed the ranking order of 99mTc-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-N3 had the highest 2-min heart uptake among 99mTc 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 99mTc-ISboroxime-N3.

Conclusion: 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-N3 has the highest initial heart uptake with the heart retention comparable to that of 99mTc-Teboroxime. 99mTc-ISboroxime-N3 is a promising alternative to 99mTc-Teboroxime for SPECT MPI.

Keywords: (99m)Tc radiotracers; (99m)Tc-Teboroxime derivatives; heart imaging.

MeSH terms

  • Animals
  • Heart / diagnostic imaging*
  • Image Processing, Computer-Assisted
  • Myocardium / metabolism
  • Organotechnetium Compounds* / chemistry
  • Organotechnetium Compounds* / metabolism
  • Organotechnetium Compounds* / pharmacokinetics
  • Oximes* / chemistry
  • Oximes* / metabolism
  • Oximes* / pharmacokinetics
  • Radioactive Tracers
  • Radiochemistry
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon / methods*


  • Organotechnetium Compounds
  • Oximes
  • Radioactive Tracers