Imaging of bacterial infections with 99mTc-labeled human neutrophil peptide-1.
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 microg (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 (IgG), 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 min, respectively. Similar half-lives were observed for 99mTc-IgG 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-IgG 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-IgG. To obtain insight into factors that contribute to accumulation of 99mTc-HNP-1 at sites of infection, the binding of this tracer to bacteria 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-IgG.


CONCLUSIONS
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.
Welling
M M
MM
Department of Radiology, Leiden University Medical Center, The Netherlands.
Nibbering
P H
PH
Paulusma-Annema
A
A
Hiemstra
P S
PS
Pauwels
E K
EK
Calame
W
W
D000818:Animals; D023082:Defensins; D006614:Hindlimb; D007074:Immunoglobulin G / Q000378:metabolism / Q000494:pharmacology; D007710:Klebsiella Infections / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000302:isolation & purification; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D009135:Muscular Diseases / Q000000981:diagnostic imaging; D010532:Peritoneal Diseases / Q000000981:diagnostic imaging; D011506:Proteins / Q000378:metabolism / Q000494:pharmacology; D011877:Radionuclide Imaging; D013203:Staphylococcal Infections / Q000000981:diagnostic imaging* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000302:isolation & purification; D013667:Technetium; D023084:alpha-Defensins
D023082:Defensins; D007074:Immunoglobulin G; D011506:Proteins; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; D013667:Technetium