Uruguayan Centre of Molecular Imaging, Montevideo, Uruguay
Uruguayan Centre of Molecular Imaging, Montevideo, Uruguay.
J Nucl Med. 2016 Apr;57(4):622-7. doi: 10.2967/jnumed.115.161265. Epub 2016 Jan 14.
The cationic peptide (68)Ga-NOTA-UBI-29-41 was synthesized and characterized. Biodistribution and PET/CT examinations were performed for evaluation of its biologic behavior. Differentiation of infection from sterile inflammation was investigated using microbiology methods at the sites of bacterial infections.
Labeling of UBI-29-41 conjugated with NOTA with (68)Ga was optimized at 20°C-100°C and pH 3.5-5.5. Radiochemical purity, stability up to 260 min, and binding to serum proteins were determined. In vitro binding to Staphylococcus aureus was evaluated from 9.14 × 10(7) to 1.17 × 10(10) cfu/mL. Of 3 groups of Mus musculus Swiss male mice, the first was inoculated intramuscularly with 1.2 × 10(8) cfu of S. aureus to provoke infection, and the second, with 1.2 × 10(8) cfu of heat shock-treated S. aureus to generate sterile inflammation. The third mouse was not treated and served as a control. After 24 h, (68)Ga-NOTA-UBI-29-41 was administrated intravenously, and biodistribution was performed at 30, 60, and 120 min. PET/CT dynamic studies (120 min) were acquired. Sinograms were reconstructed using 3D maximum-likelihood expectation maximization and analyzed with software. Infected or inflamed muscles were dissected, homogenized, and cultured in tryptic soy agar medium. Recovered S. aureus was calculated as cfu/g.
(68)Ga-NOTA-UBI-29-41 showed high renal excretion (83.2% ± 7.3%) of injected dose and rapid blood clearance. More than 95% was bound in vitro to 5 × 10(9) cfu/mL. A significantly higher (P< 0.05) accumulation of (68)Ga-NOTA-UBI-29-41 was observed at sites of S. aureus inoculation in infected mice (ratio of target to nontarget, 5.0 at 60 min and 4.1 at 120 min) compared with animals with inflammation (ratio of target to nontarget, 1.6 at 60 min and 1.2 at 120 min).
The difference in uptake of (68)Ga-NOTA-UBI-29-41 in the infected muscles compared with the inflamed muscles was clearly observed in the PET/CT images and positively correlated with the degree of infection.
合成并表征带正电荷的肽（68）Ga-NOTA-UBI-29-41。通过微生物学方法在细菌感染部位进行评估，进行生物分布和 PET/CT 检查以研究其生物学行为。
在 20°C-100°C 和 pH 3.5-5.5 下优化 NOTA 偶联 UBI-29-41 的标记。测定放射性化学纯度、260 分钟内的稳定性以及与血清蛋白的结合。从 9.14×10(7)到 1.17×10(10)cfu/mL 评估金黄色葡萄球菌的体外结合。将 3 组雄性瑞士小鼠中的第一组肌肉内接种 1.2×10(8)cfu 金黄色葡萄球菌以引发感染，第二组接种 1.2×10(8)cfu 热休克金黄色葡萄球菌以产生无菌性炎症。第三只老鼠未处理，作为对照。24 小时后，静脉内给予（68）Ga-NOTA-UBI-29-41，并在 30、60 和 120 分钟时进行生物分布。进行 PET/CT 动态研究（120 分钟）。使用 3D 最大似然期望最大化重建正弦图，并使用软件进行分析。分离、匀浆并在胰蛋白酶大豆琼脂培养基中培养受感染或发炎的肌肉。以 cfu/g 计算回收的金黄色葡萄球菌。
（68）Ga-NOTA-UBI-29-41 显示出高的肾脏排泄（83.2%±7.3%）的注射剂量和快速的血液清除。体外超过 95%与 5×10(9)cfu/mL 结合。与炎症动物（60 分钟时的靶标与非靶标比为 1.6，120 分钟时为 1.2）相比，在感染小鼠的金黄色葡萄球菌接种部位观察到（68）Ga-NOTA-UBI-29-41 的摄取明显更高（60 分钟时的靶标与非靶标比为 5.0，120 分钟时为 4.1）。
在 PET/CT 图像中清楚地观察到受感染肌肉与发炎肌肉之间（68）Ga-NOTA-UBI-29-41 的摄取差异，并且与感染程度呈正相关。
