(99m)Tc-E-selectin binding peptide for imaging acute osteomyelitis in a novel rat model.
BACKGROUND
In the present study, (99m)Tc-radiolabelled E-selectin binding peptide ((99m)Tc-IMP-178) was investigated for its potential to image acute pyogenic osteomyelitis in a new animal model. Intraindividual comparisons were performed using an irrelevant peptide ((99m)Tc-IMP-100) to demonstrate specificity.


METHODS
An acute pyogenic osteomyelitis was induced by injecting 0.05 ml of 5% sodium morrhuate and 5x10(8) CFU of Staphylococcus aureus into the medullary cavity of the right tibia in 16 rats. Sixteen additional rats served as untreated controls. Whole-body imaging of pyogenic (n=4) and untreated (n=4) animals was performed continuously during the first 8 h (12 MBq i.v. of (99m)Tc-IMP-178 and (99m)Tc-IMP-100 for control), and one further single image was acquired after 16 h p.i. Tissue biodistribution studies were performed in 12 rats with an acute pyogenic osteomyelitis and in 12 untreated rats 1, 4 and 24 h after injection. Data of the histological/radiological and haematological investigations were obtained in all animals.


RESULTS
Histopathologically, 15 of 16 treated rats (93%) developed an acute pyogenic osteomyelitis showing a major infiltration of the bone marrow by polymorphonuclear leukocytes as well as the formation of sequestra. Haematologically, the number of leukocytes increased by 100%, the lymphocytes by 11% and the granulocytes decreased by 39%. After i.v. injection, (99m)Tc-IMP-178 rapidly cleared from the body resulting in good scintigraphic target-to-background (T/B) ratios. The highest uptake of the tracer in the pyogenic bone was observed at 60 min p.i. (0.43+/-0.02% ID.g-1 for (99m)Tc-IMP-178 and 0.30+/-0.02% ID.g-1 for (99m)Tc-IMP-100), resulting in a higher osteomyelitis-to-healthy collateral ratio with T/B of 2.40+/-0.65 ((99m)Tc-IMP-178) compared with 1.85+/-0.48 ((99m)Tc-IMP-100). No adverse reactions were seen after injection of (99m)Tc-IMP-178.


CONCLUSIONS
(99m)Tc-IMP-178 allows imaging of an acute osteomyelitic lesions, presumably by interaction of (99m)Tc-IMP-178 with activated upregulated vascular endothelium.
Gratz
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S
Department of Nuclear Medicine, Philipps University of Marburg, Baldingerstrasse, 35033 Marburg, Germany. gratz@mailer.uni-marburg.de
Béhé
M
M
Boerman
O C
OC
Kunze
E
E
Schulz
H
H
Eiffert
H
H
O'Reilly
T
T
Behr
T M
TM
Angerstein
C
C
Nebendahl
K
K
Kauer
F
F
Becker
W
W
D000208:Acute Disease; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D019040:E-Selectin / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D010019:Osteomyelitis / Q000097:blood / Q000000981:diagnostic imaging* / Q000473:pathology; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D013667:Technetium; D014018:Tissue Distribution
D002352:Carrier Proteins; D019040:E-Selectin; D013667:Technetium