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Imaging of Bacterial Infections with ^99mTc-Labeled Human Neutrophil Peptide-1

Department of Radiology, Division of Nuclear Medicine
Departments of Infectious Diseases and Pulmonology, Leiden University Medical Center, Leiden
Hercules European Research Center, Barneveld, The Netherlands

Correspondence: For correspondence contact: Ernest K.J. Pauwels, Department of Radiology, Division of Nuclear Medicine, C4-Q, Leiden University Medical Center (LUMC), P.O. Box 9600, 2300 RC Leiden, The Netherlands.

ABSTRACT

This study was undertaken to evaluate whether ^99mTc-labeled human neutrophil peptide (HNP)-1 can be used as a tracer for rapid visualization of bacterial infections. Methods: Mice were injected intramuscularly with 1 million Staphylococcus aureus or Klebsiella pneumoniae organisms and 5 min later were injected intravenously with 0.4 µg (0.8 MBq) ^99mTc-HNP-1. At various intervals, detailed information about clearance and accumulation of this tracer at sites of infection and in various organs was obtained by scintigraphy. ^99mTc-labeled immunoglobulin G(lgG), an established marker of infection and inflammation, was used for comparison. Results: After injection into S. aureus- or K. pneumoniae-injected mice, ^99mTc-HNP-1 was rapidly removed from the circulation, mainly through the kidneys and bladder, with half-lives of 170 and 55 mm, respectively. Similar half-lives were observed for ^99mTc-lgG in these animals. Visualization of foci with S. aureus or K. pneumoniae, as indicated by a ratio of 1.3 or higher between the targeted thigh muscle (containing bacteria) and the nontargeted (contralateral) thigh muscle (T/NT), was already achieved 5 min after injection of ^99mTc-HNP-1. Similar T/NTs for ^99mTc-lgG were obtained 4 h after injection of the tracer, indicating that imaging of foci of bacteria with ^99mTc-HNP-1 is much faster than with ^99mTc-lgG. To obtain insight into factors that contribute to accumulation of ^99mTc-HNP-1 at sites of infection, the binding of this tracer to bacterial and leukocytes was assessed using a peritoneal infection model. Binding of ^99mTc-HNP-1 to bacteria was approximately 1000 times higher than binding to leukocytes. Although the number of bacteria in the peritoneum was 1000-fold lower than the number of leukocytes, a significant correlation between binding of ^99mTc-HNP-1 to bacteria on the one hand and accumulation of tracer on the other was still found, in contrast to ^99mTc-lgG. Conclusion: ^99mTc HNP-1 allows rapid visualization of bacterial infections. Binding of this tracer to bacteria most likely contributes significantly to the accumulation of ^99mTc-HNP-1 at sites of infection.

Key Words: infection imaging • bacteria • ^99mTc labeling • human neutrophil peptide-1

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