Radiolabeled Zn-DPA as a potential infection imaging agent
Department of Radiology; Department of Pathology
Animals; Biotinylation; Chelating Agents; Fluorescent Dyes; Heterocyclic Compounds, 1-Ring; Inflammation; Isotope Labeling; Lipopolysaccharides; Mice; Multimodal Imaging; Nanoparticles; Organometallic Compounds; Picolinic Acids; Positron-Emission Tomography; Streptavidin; Streptococcal Infections; Streptococcus pyogenes; Tomography, X-Ray Computed
Bacterial Infections and Mycoses | Diagnosis | Medical Pathology | Pathology | Radiology
INTRODUCTION: A zinc-dipicolylamine analog (Zn-DPA) conjugated with a fluorophore (PSVue(R)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 mug 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.
Zn-DPA, Streptavidin, Bacterial infection, Sterile inflammation, Imaging agent
DOI of Published Version
Nucl Med Biol. 2012 Jul;39(5):709-14. doi: 10.1016/j.nucmedbio.2011.12.006. Epub 2012 Feb 10. Link to article on publisher's site.
Nuclear medicine and biology
Liu, Xinrong; Cheng, Dengfeng; Gray, Brian D.; Wang, Yuzhen; Akalin, Ali; Rusckowski, Mary; Pak, Koon Y.; and Hnatowich, Donald J., "Radiolabeled Zn-DPA as a potential infection imaging agent" (2012). Radiology Publications and Presentations. 108.