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

Abstract

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 ± 0.4 min for 99mTc-ISboroxime-N3, 0.7 ± 0.1 min for 99mTc-PYboroxime-N3 and 0.9 ± 0.4 min 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 0–5 min 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.

Novel 99mTc(III) Complexes [99mTcCl(CDO)(CDOH)2B–R] (CDOH2 = Cyclohexanedione Dioxime) Useful as Radiotracers for Heart Imaging

“…Previously, we used the fast-phase half-life, which indicates the rate of heart radioactivity change, to evaluate the myocardial retention of 99m Tc­(III) radiotracers because their myocardial washout curves were all fitted the bi-exponential equation. ,− In this study, we found that the AUC value is a much better indicator than the fast-phase half-life. Longer myocardial retention time does not necessarily indicate a better radiotracer if its initial heart uptake is low.…”

“…All new 99m Tc­(III) complexes [ 99m TcCl­(CDO)­(CDOH) 2 B–R] (R = 2F, 3F, 5F, HP, MPY, PM, and 4PY) were prepared according to Chart using the kit formulation. − Table lists radiochemical purity (RCP) data and HPLC retention times of 99m Tc–Teboroxime and new 99m Tc­(III) radiotracers [ 99m TcCl­(CDO)­(CDOH) 2 B–R] (R = 2F, 3F, 5F, HP, MPY, PM, and 4PY). The RCP values were 95–98% for new radiotracers [ 99m TcCl­(CDO)­(CDOH) 2 B–R] (R = 3F, 5F, HP, MPY, PM, and 4PY), with the radioimpurity being <2% (Figure SI1).…”

“…Complexes [ 99m TcCl­(CDO)­(CDOH) 2 B–R] (R = 2F, 3F, 5F, HP, MPY, PM, and 4PY) were prepared using the kit formulation. − Each lyophilized vial contains 2 mg of CDOH 2 , 4–5 mg of boronic acid, 50 μg of SnCl 2 ·2H 2 O, 9 mg of citric acid, 2 mg of DTPA, 20 mg of NaCl, and 20 mg of γ-cyclodextrin. A total of 1.0 mL of 99m TcO 4 – solution (370–1110 MBq) was added to a lyophilized vial.…”

“…We have been interested in 99m Tc­(III) complexes [ 99m TcL­(CDO)­(CDOH) 2 B–R] (L = Cl, F, N 3 and SCN; R = alkyls or aryls) as radiotracers for MPI − because 99m Tc–Teboroxime has a high first-pass extraction fraction and shows the linear relationship between its heart uptake and the regional blood flow rate up to 5 mL/min/g at 1–2 min p.i . In this report, we present the evaluation of complexes [ 99m TcCl­(CDO)­(CDOH) 2 B–R] (Figure : R = 2F, 3F, 5F, HP, MPY, PM, and 4PY) for their potential as radiotracers for heart imaging.…”

Novel Approach for 99mTc-Labeling of Red Blood Cells: Evaluation of 99mTc-4SAboroxime as a Blood Pool Imaging Agent

“…We have been interested in 99m Tc­(III) complexes [ 99m TcCl­(CDO)­(CDOH) 2 B-R] (Figure : CDOH 2 = cyclohexanedione dioxime; R = alkyl or aryl groups) as radiotracers for heart imaging. − Recently, we found that the complex [ 99m TcCl­(CDO)­(CDOH) 2 B-4S] (Figure : 99m Tc-4Sboroxime, 4S-B­(OH) 2 = 4-(methanesulfonyl)­phenylboronic acid) is an excellent heart imaging agent . However, its liver uptake is high .…”