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

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• 作者：Min Liu^a ; ^b ; Yumin Zheng^c ; Ugur Avcibasi^b ; ^d ; Shuang Liu^b ; ^{liu100@purdue.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：CAD ; coronary artery disease ; CT ; computed tomography ; CZT ; cadmium-zinc-telluride ; DTPA ; diethylenetriaminepentaacetic acid ; ITLC ; instant thin layer chromatography ; RCP ; radiochemical purity ; SPECT ; single photon-emission computed tomography ; 99mTc-ISboroxime ; [99mTcCl(CDO)(CDOH)2B-IS] (CDOH2  ; =  ; cyclohexanedione dioxime ; IS  ; =  ; isoxazol-4-yl) ; 99mTc-ISboroxime-N3 ; [99mTc(N3)(CDO)(CDOH)2B-IS] ; 99mTc-MPboroxime ; [99mTcCl(CDO)(CDOH)2B-MP] (MP  ; =  ; N-methylpyridinium-4-yl)
• 刊名：Nuclear Medicine and Biology
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：43
• 期：11
• 页码：732-741
• 全文大小：1303 K

文摘

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.