Boddeti Dilip Kumar, Kumar Vijay
Department of Nuclear Medicine and PET, Westmead Hospital, Sydney NSW, Australia.
Department of Nuclear Medicine, The Children's Hospital at Westmead, Westmead.
World J Nucl Med. 2021 Apr 10;20(3):266-272. doi: 10.4103/wjnm.WJNM_103_20. eCollection 2021 Jul-Sep.
Synthetic antimicrobial peptide fragment, Tc-Ubiquicidin 29-41, is shown to be sensitive and also specific for imaging bacterial infections. We undertook this study to explore the advantage of using a positron emission agent, Ga-DOTA-Ubiquicidin 29-41 (Ga-DOTA-UBI), for detecting Staph-A infection in an animal model, and also evaluated its ability to distinguish a turpentine-induced sterile inflammation in an animal model. Pure Ga-68 was freshly eluted from a Ge/Ga generator (IGG-100). DOTA-UBI (50 μg) was ra diolabeled with pure Ga-68 (500MBq) by incubating the reaction mixture at pH 4.5 for 10 min, 95°C. Rats were infected with Staph-A at the hind leg joint of rats to form bacterial abscess. Sterile inflammation was induced in the right thigh muscle by injecting 200 μl of 100% turpentine oil. Rats were injected intravenously with 10-15 MBq of tracer, and images were acquired at different time intervals with Siemens (Biograph mCT) positron emission tomography computed tomography scanner. The early images at 6 min postinjection clearly indicated mild uptake of the agent corresponding to the infection site, which increased dramatically at 20, 30, and 60 min postinjection. The target to background ratio (T/B) increased significantly over the same time period of study (1.6, 4.2, and 6.1, respectively). There was a mild uptake of Ga-DOTA-UBI at the site corresponding to sterile inflammation at 6 min postinjection, which was rapidly washed off as seen at 25 and 45 min images. The images indicated fast clearance of the agent from liver and soft tissues within 6 min. Control rats showed similar biodistribution of activity. The mild uptake of Ga-DOTA-UBI at the corresponding Staph-A infection lesion and very fast kinetics of clearance from the blood pool and soft tissues suggested a very high clinical potential for this agent. The absence of uptake of the agent at sterile inflammation site suggests that the agent may be useful in distinguishing infection from inflammation.
合成抗菌肽片段Tc-Ubiquicidin 29-41已被证明对细菌感染成像敏感且具有特异性。我们开展这项研究以探索使用正电子发射剂Ga-DOTA-Ubiquicidin 29-41（Ga-DOTA-UBI）在动物模型中检测金黄色葡萄球菌感染的优势，并评估其区分动物模型中松节油诱导的无菌性炎症的能力。纯Ga-68从锗/镓发生器（IGG-100）中新鲜洗脱。通过将反应混合物在pH 4.5、95°C下孵育10分钟，用纯Ga-68（500MBq）对DOTA-UBI（50μg）进行放射性标记。在大鼠后腿关节处感染金黄色葡萄球菌以形成细菌性脓肿。通过注射200μl 100%松节油在右大腿肌肉中诱导无菌性炎症。给大鼠静脉注射10 - 15MBq示踪剂，并使用西门子（Biograph mCT）正电子发射断层扫描计算机断层扫描仪在不同时间间隔采集图像。注射后6分钟的早期图像清楚地显示对应感染部位有轻度的示踪剂摄取，在注射后20、30和60分钟时显著增加。在同一研究时间段内，靶本底比（T/B）显著增加（分别为1.6、4.2和6.1）。注射后6分钟时，在对应无菌性炎症的部位有轻度的Ga-DOTA-UBI摄取，如在25分钟和45分钟图像中所见，其很快被清除。图像显示示踪剂在6分钟内从肝脏和软组织中快速清除。对照大鼠显示出相似的放射性分布。Ga-DOTA-UBI在相应的金黄色葡萄球菌感染病灶处有轻度摄取，且从血池和软组织中清除的动力学非常快，这表明该制剂具有很高的临床潜力。该制剂在无菌性炎症部位无摄取，表明该制剂可能有助于区分感染与炎症。
