Liu Min, Fang Wei, Liu Shuang
Department of Radiation Medicine and Protection, Medical College, Soochow University , China.
School of Health Sciences, Purdue University , Indiana 47907, United States.
Bioconjug Chem. 2016 Nov 16;27(11):2770-2779. doi: 10.1021/acs.bioconjchem.6b00552. Epub 2016 Oct 24.
In this study, we evaluated seven new Tc(III) complexes [TcCl(CDO)(CDOH)B-R] (Tc-2Fboroxime: R = 2-formylfuran-3-yl (2F); Tc-3Fboroxime: R = furan-3-yl (3F); Tc-5Fboroxime: R = 5-formyfuran-2-yl (5F); Tc-HPboroxime: R = 6-hydroxylpyridin-2-yl (HP); Tc-MPYboroxime: R = 5-methoxypyridin-3-yl (MPY); Tc-PMboroxime: R = 1,5-pyrimidin-3-yl (PM); and Tc-4PYboroxime: R = pyridin-4-yl (4PY)) for their potential as heart imaging agents. All new Tc(III) radiotracers except Tc-2Fboroxime were prepared with high radiochemical purity (RCP > 95%). The low RCP (∼75%) for Tc-2Fboroxime is most likely caused by steric hindrance from the 3-formyl group. Biodistribution and imaging studies were performed in SD rats. Planar image quantification was performed to compare their myocardial retention times. We found that the myocardial washout curves of new Tc(III) radiotracers were best fitted the biexponential decay function. The AUC (area under the curve) values followed the general trend: Tc-5Fboroxime (129 ± 6) > Tc-3Fboroxime (114 ± 11) > Tc-Teboroxime (104 ± 16) > Tc-MPYboroxime (92 ± 18) > Tc-4PYboroxime (77 ± 10) > Tc-PMboroxime (68 ± 14) ≈ Tc-HPboroxime (62 ± 14). The 2 min heart uptake values from biodistribution studies follow the ranking order of Tc-5Fboroxime (3.75 ± 0.15%ID/g) ≈ Tc-MPYboroxime (3.73 ± 0.24%ID/g) > Tc-PMboroxime (3.47 ± 0.15%ID/g) ≈ Tc-3Fboroxime ≈ (3.25 ± 0.77%ID/g). The 5 min heart uptake of Tc-5Fboroxime (3.91 ± 0.09%ID/g) was almost identical to its 2 min heart uptake (3.75 ± 0.15%ID/g), and its 15 min heart uptake value (2.83 ± 0.08%ID/g) compared well to the 2 min heart uptake of Tc-Teboroxime (3.00 ± 0.37%ID/g). It took ∼5 min for Tc-5Fboroxime to approach the 1 min heart uptake value of Tc-Teboroxime (∼3.5% ID/g) and ∼9.5 min to reach the 2 min heart uptake value of Tc-Teboroxime (∼3.0% ID/g). The best image acquisition window is 0-5 min for Tc-5Fboroxime. High-quality single-photon emission computed tomography images of the rat hearts were acquired in any of the 5 min window over the first 20 min after its administration. Tc-5Fboroxime has significant advantages over Tc-Teboroxime as the radiotracer for myocardial perfusion imaging.
在本研究中，我们评估了七种新型锝（III）配合物[TcCl(CDO)(CDOH)B-R]（锝-2F硼肟：R = 2-甲酰基呋喃-3-基（2F）；锝-3F硼肟：R = 呋喃-3-基（3F）；锝-5F硼肟：R = 5-甲酰基呋喃-2-基（5F）；锝-HP硼肟：R = 6-羟基吡啶-2-基（HP）；锝-MPY硼肟：R = 5-甲氧基吡啶-3-基（MPY）；锝-PM硼肟：R = 1,5-嘧啶-3-基（PM）；以及锝-4PY硼肟：R = 吡啶-4-基（4PY））作为心脏成像剂的潜力。除锝-2F硼肟外，所有新型锝（III）放射性示踪剂的放射化学纯度均较高（RCP > 95%）。锝-2F硼肟的低RCP（约75%）很可能是由3-甲酰基的空间位阻引起的。在SD大鼠中进行了生物分布和成像研究。进行平面图像定量以比较它们的心肌保留时间。我们发现新型锝（III）放射性示踪剂的心肌洗脱曲线最适合双指数衰减函数。曲线下面积（AUC）值遵循一般趋势：锝-5F硼肟（129±6）>锝-3F硼肟（114±11）>锝-替硼肟（104±16）>锝-MPY硼肟（92±18）>锝-4PY硼肟（77±10）>锝-PM硼肟（68±14）≈锝-HP硼肟（62±14）。生物分布研究中2分钟时的心脏摄取值遵循以下排序：锝-5F硼肟（3.75±0.15%ID/g）≈锝-MPY硼肟（3.73±0.24%ID/g）>锝-PM硼肟（3.47±0.15%ID/g）≈锝-3F硼肟≈（3.25±0.77%ID/g）。锝-5F硼肟5分钟时的心脏摄取（3.91±0.09%ID/g）与其2分钟时的心脏摄取（3.75±0.15%ID/g）几乎相同，其15分钟时的心脏摄取值（2.83±0.08%ID/g）与锝-替硼肟2分钟时的心脏摄取（3.00±0.37%ID/g）相当。锝-5F硼肟约需5分钟达到锝-替硼肟1分钟时的心脏摄取值（约3.5%ID/g），约9.5分钟达到锝-替硼肟2分钟时的心脏摄取值（约3.0%ID/g）。锝-5F硼肟的最佳图像采集窗口为0 - 5分钟。在给药后的前20分钟内，在5分钟的任何时间段都能获得大鼠心脏的高质量单光子发射计算机断层扫描图像。作为心肌灌注成像的放射性示踪剂，锝-5F硼肟比锝-替硼肟具有显著优势。
