Impact of Boronate Capping Groups on Biological Characteristics of Novel 99mTc(III) Complexes [99mTcCl(CDO)(CDOH)2B-R] (CDOH2 = Cyclohexanedione Dioxime)
Abstract
This study sought to explore the impact of boronate groups on the heart uptake and myocardial retention of novel 99mTc(III) complexes [99mTcCl(CDO)(CDOH)2B-R] (99mTc-ISboroxime: R = isoxazol-4-yl (IS); 99mTc-MPboroxime: R = N-methylpyridinium (MP); 99mTc-PAboroxime: R = pyrazol-3-yl (PA); 99mTc-PYboroxime: R = pyridin-3-yl (PY); and 99mTc-5Uboroxime: R = uracil-5-yl (5U)). All five new 99mTc(III) radiotracers were prepared in high yield and high radiochemical purity (RCP = 90–98%), and they remained stable in the kit mixture for >6 h. Biodistribution and imaging (planar and SPECT) studies were carried out using Sprague–Dawley (SD) rats. Planar image quantification was performed to compare their myocardial retention and liver clearance kinetics. It was found that their heart retention and liver clearance curves were best fitted to the biexponential decay function. The initial heart uptake at 0–1 min after injection followed the general ranking order of 99mTc-ISboroxime (4.98 ± 1.05%ID) ∼ 99mTc-Teboroxime (4.56 ± 0.91%ID) ∼ 99mTc-PAboroxime (4.03 ± 1.23%ID) ∼ 99mTc-PYboroxime (4.07 ± 0.80%ID) > 99mTc-5Uboroxime (3.24 ± 0.67%ID) > 99mTc-MPboroxime (2.53 ± 0.65%ID). The fast-phase myocardial retention time followed the general order of 99mTc-PAboroxime (3.21 ± 0.29 min) > 99mTc-Teboroxime (1.63 ± 0.40 min) ∼ 99mTc-PYboroxime (1.57 ± 0.29 min) ∼ 99mTc-ISboroxime (1.55 ± 0.32 min) > 99mTc-MPboroxime (0.68 ± 0.16 min) > 99mTc-5Uboroxime (0.33 ± 0.11 min). 99mTc-PAboroxime (3.05 ± 1.10%ID/g) and 99mTc-ISboroxime (3.75 ± 0.68%ID/g) had the 2 min initial heart uptake very close to that of 99mTc-Teboroxime (3.30 ± 0.50%ID/g). However, the myocardial retention time of 99mTc-PAboroxime was significantly longer than that of 99mTc-ISboroxime and 99mTc-Teboroxime. Even though the best time window is 0–5 min for SPECT image acquisition, high quality SPECT images could be obtained during the first 30 min postinjection of 99mTc-PAboroxime in SD rats. This statement was supported by the SPECT/CT studies in normal pigs. On the basis of results from this study, it was concluded that boronate groups had significant impact on the heart uptake, myocardial retention, and liver clearance kinetics of 99mTc(III) complexes [99mTcCl(CDO)(CDOH)2B-R]. The combination of high initial heart uptake with longer myocardial retention makes it possible to image the heart with 99mTc-PAboroxime during the first 30 min using both standard and specialized cardiac SPECT cameras.
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