Radiolabeled Zn-DPA as a potential infection imaging agent.
BACKGROUND
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.
Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Xinrong
X
Liu
Dengfeng
D
Cheng
Brian D
BD
Gray
Yuzhen
Y
Wang
Ali
A
Akalin
Mary
M
Rusckowski
Koon Y
KY
Pak
Donald J
DJ
Hnatowich
D000818:Animals; D019921:Biotinylation; D002614:Chelating Agents / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D007249:Inflammation / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D007553:Isotope Labeling; D008070:Lipopolysaccharides / Q000009:adverse effects; D051379:Mice; D064847:Multimodal Imaging; D053758:Nanoparticles / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D010848:Picolinic Acids / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D019809:Streptavidin / Q000378:metabolism; D013290:Streptococcal Infections / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D013297:Streptococcus pyogenes / Q000472:pathogenicity*; D014057:Tomography, X-Ray Computed
D002614:Chelating Agents; D005456:Fluorescent Dyes; D006573:Heterocyclic Compounds, 1-Ring; D008070:Lipopolysaccharides; D009942:Organometallic Compounds; D010848:Picolinic Acids; C529174:bis-dipicolylamine-Zinc(II); C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D019809:Streptavidin