[99mTc]cFLFLF for Early Diagnosis and Therapeutic Evaluation in a Rat Model of Acute Osteomyelitis
[99mTc]cFLFLF for Early Diagnosis and Therapeutic Evaluation in a Rat Model of Acute Osteomyelitis
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[99mTc]cFLFLF 用于急性骨髓炎大鼠模型的早期诊断和治疗评估
DOI：
10.1007/s11307-014-0787-3
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发表时间：
2015-06-01
影响因子：
3.1
通讯作者：
Xiong, Wei
中科院分区：
文献类型：
--
作者：
Chen, Jing;Cheng, Hao;Xiong, Wei
目的急性骨髓炎（AO）的早期诊断和治疗监测具有挑战性。在此，我们使用聚乙二醇（PEG）化的趋化肽肉桂酰-F-（D）L-F-（D）L-F（cFLFLF）与肼基烟酰胺（HYNIC）缀合并用Tc-99 m（[99 mTc]cFLFLF）标记以在大鼠模型中成像AO并验证其在AO的早期诊断和治疗评估中的功效。A、B、C、G、H组为AO模型组，D、E、F组为假手术对照组。A组和D组进行[99 mTc]cFLFLF骨显像，B组和E组进行[99 mTc]亚甲基二膦酸盐（[99 mTc]MDP）骨扫描，C组和F组进行2-脱氧-2-[18 F]氟-d-葡萄糖（[18 F]FDG）正电子发射断层扫描（PET）/计算机断层扫描（CT）。在G组中评估[99 mTc]cFLFLF的生物分布。H组采用[99 mTc]cFLFLF放射性核素显像评价抗生素治疗的疗效。常规X线摄影后获得。计算感染或假手术胫骨与对侧胫骨的比值（T/B）。影像学检查结束后，立即切除感染的胫骨，进行组织病理学分析和免疫组化染色.ResultsAO在A、B、C、G和H组的所有大鼠中均存在。A、B和C组的总组织学评分无显著差异（F= 0.34，p = 0.71）。生物分布结果显示，[99 mTc]cFLFLF在感染胫骨中显著摄取和良好保留。[99 mTc]cFLFLF骨显像和[99 mTc]MDP骨扫描均检出AO。注射后1h [99 mTc]cFLFLF骨显像的T/B比值是[99 mTc]MDP骨显像的2.09倍（t= 13.81，p <0.001）。[18 F]FDG PET/CT扫描的平均T/B比与对照组F无显著差异（t= 2.17，p = 0.062）。[99 mTc]cFLFLF荧光造影显示，H组的炎症显着衰减后3周的抗生素治疗，这是由组织病理学分析和免疫组化staining.ConclusionOur结果表明，特异性和图像质量的[99 mTc]cFLFLF是上级的[99 mTc]MDP和[18 F]DFG成像探针目前用于AO的早期诊断。此外，[99 mTc]cFLFLF能够有效地评估AO对抗生素治疗的治疗反应。我们的数据表明，[99 mTc]cFLFLF是一种很有前途的显像剂，用于检测感染性疾病。
PurposeEarly diagnosis and therapeutic monitoring of acute osteomyelitis (AO) is challenging. Here, we use a polyethylene glycol (PEG)ylated chemotactic peptide cinnamoyl-F-(D)L-F-(D)L-F (cFLFLF) conjugated with hydrazinonicotinamide (HYNIC) and labeled with Tc-99m ([99mTc]cFLFLF) to image AO in a rat model and to validate its efficacy in early diagnosis and therapeutic evaluation of AO.ProceduresForty rats were divided into eight groups of five each. Groups A, B, C, G, and H were AO models, and D, E, and F were sham controls. Groups A and D underwent [99mTc]cFLFLF scintigraphy, groups B and E underwent [99mTc]methylene diphosphonate ([99mTc]MDP) bone scan, and groups C and F underwent 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) positron emission tomography (PET)/computed tomography (CT) scan. [99mTc]cFLFLF biodistribution was assessed in group G. The response to antibiotic therapy was evaluated using [99mTc]cFLFLF scintigraphy in group H. Conventional radiographs were obtained following scintigraphy. Ratios of infected or sham-operated tibia to the opposite tibia (T/B) were calculated. Immediately after the imaging studies, infected tibias were excised and underwent histopathological analysis and immunohistochemistry staining.ResultsAO was present in all rats of groups A, B, C, G, and H. Total histological scores were not significantly different among groups A, B, and C (F= 0.34,p= 0.71). The biodistribution results revealed significant uptake and excellent retention of [99mTc]cFLFLF in the infected tibia. [99mTc]cFLFLF scintigraphy and [99mTc]MDP bone scan both detected AO. The mean T/B ratio of [99mTc]cFLFLF scintigraphy 1 h postinjection was 2.09-fold higher than that of [99mTc]MDP bone scan (t= 13.81,p<0.001). The mean T/B ratio of [18F]FDG PET/CT scan was not significantly different from the control group F (t= 2.17,p= 0.062). [99mTc]cFLFLF scintigraphy revealed a significant attenuation of inflammation in group H following a 3-week antibiotic treatment, which was verified by histopathological analysis and immunohistochemistry staining.ConclusionOur results suggest that the specificity and image quality of [99mTc]cFLFLF are superior to those of the [99mTc]MDP and [18F]DFG imaging probes currently used for early diagnosis of AO. Furthermore, [99mTc]cFLFLF was able to effectively evaluate the therapeutic response to antibiotic treatment of AO. Our data suggest that [99mTc]cFLFLF is a promising imaging agent for detection of infectious diseases.