Ebenhan Thomas, Zeevaart Jan Rijn, Venter Jacobus D, Govender Thavendran, Kruger Gert H, Jarvis Neil V, Sathekge Mike M
Department of Nuclear Medicine, University of Pretoria and Steve Biko Academic Hospital, Pretoria, South Africa.
J Nucl Med. 2014 Feb;55(2):308-14. doi: 10.2967/jnumed.113.128397. Epub 2014 Jan 16.
Antimicrobial peptides such as ubiquicidin (UBI) are believed to differentiate between mammalian and bacterial or fungal cells. (99m)Tc-UBI29-41 was previously tested for detecting infection in humans using SPECT. For the present study, the UBI fragment UBI29-41 (TGRAKRRMQYNRR) was conjugated to 1,4,7-triazacyclononane-triacetic acid (NOTA), radiolabeled with (68)Ga, and investigated in a rabbit infection model.
(68)Ga was obtained from a 1.85-GBq (68)Ge/(68)Ga generator. New Zealand White rabbits were anesthetized with ketamine/medetomidine before tracer administration and placed in a clinical PET/CT scanner. (68)Ga-1,4,7-triazacyclononane-1,4,7-triacetic-acid-ubiquicidin29-41 ((68)Ga-NOTA-UBI29-41) was formulated in saline solution, and 101 ± 41 MBq were administered intravenously. The tracer distribution was studied by PET/CT imaging in animals (a) that were healthy, (b) bearing muscular Staphylococcus aureus infections and turpentine oil-induced muscular inflammations, and (c) bearing ovalbumin-induced lung inflammations. Static PET/CT imaging was performed at different time intervals up to 120 min after injection. For calculation of target-to-nontarget ratios, standardized uptake values were normalized against healthy thigh muscle, representing nontargeted tissue.
PET/CT images of healthy animals showed predominant distribution in the kidneys, liver, and bladder; heart and spleen showed moderate, declining uptake, only. The biologic half-life in blood was 29 min. Urinary accumulation of (68)Ga-NOTA-UBI29-41 peaked at 3.8 ± 0.91 percentage injected dose per gram (%ID) at 120 min, and 88 ± 5.2 %ID was recovered in total urine. (68)Ga-NOTA-UBI29-41 imaging in (b) selectively visualized the muscular infection site and was differentiated from sterile inflammatory processes. Standardized uptake value ratios for muscles (infected/inflamed) were 2.9 ± 0.93, 2.9 ± 0.50, 3.5 ± 0.86, and 3.8 ± 0.90 at 5, 30, 60, and 90 min after injection, respectively. Rabbit lungs with asthma showed insignificant uptake.
(68)Ga-NOTA-UBI29-41 was strongly localized in bacteria-infected areas and minimally detected in a sterile inflammation area in rabbit muscles. The findings propose this compound to be an excellent first-line PET/CT tracer to allow the distinguishing of infection from inflammation.
抗菌肽如泛杀菌素（UBI）被认为能够区分哺乳动物细胞与细菌或真菌细胞。此前已对（99m）Tc-UBI29-41进行了使用单光子发射计算机断层扫描（SPECT）检测人类感染的测试。在本研究中，将UBI片段UBI29-41（TGRAKRRMQYNRR）与1,4,7-三氮杂环壬烷-三乙酸（NOTA）偶联，用（68）Ga进行放射性标记，并在兔感染模型中进行研究。
（68）Ga由一台1.85GBq的（68）Ge/（68）Ga发生器获得。在给予示踪剂前，用氯胺酮/美托咪定对新西兰白兔进行麻醉，并将其置于临床正电子发射断层显像/X线计算机体层成像（PET/CT）扫描仪中。（68）Ga-1,4,7-三氮杂环壬烷-1,4,7-三乙酸-泛杀菌素29-41（（68）Ga-NOTA-UBI29-41）用生理盐水配制，静脉注射101±41MBq。通过PET/CT成像研究示踪剂在以下动物体内的分布：（a）健康动物；（b）患有肌肉金黄色葡萄球菌感染和松节油诱导的肌肉炎症的动物；（c）患有卵清蛋白诱导的肺部炎症的动物。在注射后长达120分钟的不同时间间隔进行静态PET/CT成像。为了计算靶与非靶比值，将标准化摄取值相对于代表非靶向组织的健康大腿肌肉进行归一化。
健康动物的PET/CT图像显示主要分布在肾脏、肝脏和膀胱；心脏和脾脏仅显示中等程度的、逐渐下降的摄取。血液中的生物半衰期为29分钟。（68）Ga-NOTA-UBI29-41在尿液中的蓄积在120分钟时达到峰值，为每克注射剂量的3.8±0.91%（%ID），总尿液中回收了88±5.2%ID。（b）组中（68）Ga-NOTA-UBI29-41成像选择性地显示了肌肉感染部位，并与无菌性炎症过程区分开来。注射后5、30、60和90分钟时，肌肉（感染/炎症）的标准化摄取值比值分别为2.9±0.93,2.9±0.50,3.5±0.86和3.8±0.90。患有哮喘的兔肺摄取不明显。
（68）Ga-NOTA-UBI29-41在兔肌肉中强烈定位于细菌感染区域，在无菌炎症区域中检测到的量极少。这些发现表明该化合物是一种出色的一线PET/CT示踪剂，能够区分感染与炎症。
