Radiolabeled Zn-DPA as a potential infection imaging agent

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• 作者：Xinrong Liu^a ; Dengfeng Cheng^a ; Brian D. Gray^b ; Yuzhen Wang^a ; Ali Akalin^c ; Mary Rusckowski^a ; Koon Y. Pak^b ; Donald J. Hnatowich^a ; ^{donald.hnatowich@umassmed.edu}
• 关键词：Zn-DPA ; Streptavidin ; Bacterial infection ; Sterile inflammation ; Imaging agent
• 刊名：Nuclear Medicine and Biology
• 出版年：2012
• 期刊代码：43_09698051
• 类别：ph
• 出版时间：July, 2012
• 卷：39
• 期：5
• 页码：709-714
• 文件大小：983 K

摘要

Introduction

A zinc-dipicolylamine analog (Zn-DPA) conjugated with a fluorophore (PSVue庐794) has been shown to image bacterial infections in mice. However, radiolabeled Zn-DPA has not previously been considered for nuclear imaging of infection.

Methods

Both ¹¹¹In-labeled DOTA-biotin and Zn-DPA-biotin were combined using streptavidin (SA) as a noncovalent linker. Mice injected intramuscularly with Streptococcus pyogenes (infection model) or with lipopolysaccharide (LPS) (inflammation model) were coinjected intravenously with 6 渭g of DPA as PSVue794 and as ¹¹¹In-DOTA-biotin/SA/biotin-Zn-DPA. Periodic fluorescent and SPECT (single photon emission computed tomography)/CT (computed tomography) images were acquired, and biodistributions were obtained at 22 h.

Results

Histological examination confirmed the validity of both the infection and inflammation animal models. Both the whole-body optical and nuclear images showed obvious accumulations in the target thigh in both models at all time points. At 22 h, the average target thigh accumulation of ¹¹¹In was 1.66%ID/g (S.D. 0.15) in the infection mice compared to 0.58%ID/g (S.D. 0.07) in the inflammation mice (P<.01), and the ¹¹¹In target/normal thigh ratio was 2.8 fold higher in the infection animals compared to the inflammation animals.

Conclusions

These preliminary results show that Zn-DPA within streptavidin targets S. pyogenes-infected mice similarly to its free fluorescent analogue. The significantly higher accumulation in the live bacterial infection thigh compared to that of the LPS-induced inflammation thigh suggests that Zn-DPA may be a promising imaging agent to distinguish between bacterial infections and sterile inflammations.