Radiolabeled Zn-DPA as a potential infection imaging agent.

Abstract

INTRODUCTION:

A zinc-dipicolylamine analog (Zn-DPA) conjugated with a fluorophore (PSVue®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 μg 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.

• Authors: Xinrong Liu, Dengfeng Cheng, Brian D Gray, Yuzhen Wang, Ali Akalin, Mary Rusckowski, Koon Y Pak, Donald J Hnatowich
• Journal: Nuclear medicine and biology (Nucl Med Biol) Vol. 39 Issue 5 Pg. 709-14 (Jul 2012) ISSN: 1872-9614 [Electronic] United States
• PMID: 22321532 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Published by Elsevier Inc.

Chemical References

• Chelating Agents
• Fluorescent Dyes
• Heterocyclic Compounds, 1-Ring
• Lipopolysaccharides
• Organometallic Compounds
• Picolinic Acids
• bis-dipicolylamine-Zinc(II)
• 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
• Streptavidin

Topics

• Animals
• Biotinylation
• Chelating Agents (chemistry)
• Fluorescent Dyes (chemistry)
• Heterocyclic Compounds, 1-Ring (chemistry)
• Inflammation (chemically induced, diagnostic imaging, metabolism, pathology)
• Isotope Labeling
• Lipopolysaccharides (adverse effects)
• Mice
• Multimodal Imaging
• Nanoparticles (chemistry)
• Organometallic Compounds (chemistry, metabolism, pharmacokinetics)
• Picolinic Acids (chemistry, metabolism, pharmacokinetics)
• Positron-Emission Tomography
• Streptavidin (metabolism)
• Streptococcal Infections (diagnostic imaging, metabolism, pathology)
• Streptococcus pyogenes (pathogenicity)
• Tomography, X-Ray Computed