Technetium-99m-labeled chemotactic peptides in acute infection and sterile inflammation.
Chemotactic peptides have been proposed as vehicles to image infection and inflammation. Previous studies have shown high uptake at the site of infection soon after injection, most likely because of specific binding to receptors on locally present leukocytes. To investigate this hypothesis, the in vivo behavior of a synthetic chemotactic peptide was compared to a control peptide of similar molecular weight with low receptor binding affinity. In addition, the potential to target to different infections and sterile inflammation was tested.


METHODS
Twenty-four hours after induction of Escherichia coli, Staphylococcus aureus and zymosan abscesses, rabbits were i.v. injected with either 1 mCi of 99mTc-labeled formyl-methionyl-leucyl-phenylalanyl-lysine-hydrazinonicotinamid e (99mTc-fMLFK-HYNIC) or 99mTc-labeled hydrazinonicotinamide-methionyl-leucyl-phenylalanyl-OMe (99mTc-HYNIC-MLFOMe, control peptide). Gamma camera images were obtained at 5 min and 1, 4, 8 and 20 hr postinjection. Biodistribution was determined at 20 hr postinjection.


RESULTS
The blood clearances of 99mTc-fMLFK-HYNIC and 99mTc-HYNIC-MLFOMe were similar. With time, 99mTc-fMLFK-HYNIC was retained in the abscess (E. coli), whereas the control agent 99mTc-HYNIC-MLFOMe was cleared from the abscess (0.049 +/- 0.011 versus 0.005 +/- 0.0003% 1D/g at 20 hr postinjection; p < 0.0005). Abscess-to-contralateral muscle ratios of 99mTc-fMLFK-HYNIC rose to 36.8 +/- 4.3 at 20 hr postinjection. E. coli, S. aureus and zymosan abscesses were clearly visualized from 4 hr postinjection onward. Abscess-to-background ratios increased to values varying from 4.4 +/- 0.2 (zymosan) to 7.1 +/- 0.6 (S. aureus) at 20 hr postinjection. The uptake in S. aureus and zymosan abscesses did not differ significantly from the uptake in E. coli abscesses.


CONCLUSIONS
fMLFK-HYNIC is retained in both acute infection and sterile inflammation by means of specific receptor binding if sufficient cellular infiltration is present.
van der Laken
C J
CJ
Department of Nuclear Medicine, University Hospital Nijmegen, The Netherlands.
Boerman
O C
OC
Oyen
W J
WJ
van de Ven
M T
MT
Edwards
D S
DS
Barrett
J A
JA
van der Meer
J W
JW
Corstens
F H
FH
D000038:Abscess / Q000000981:diagnostic imaging*; D000818:Animals; D002630:Chemotactic Factors / Q000493:pharmacokinetics; D002634:Chemotaxis, Leukocyte; D004927:Escherichia coli Infections / Q000000981:diagnostic imaging*; D005260:Female; D007249:Inflammation / Q000000981:diagnostic imaging*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D009842:Oligopeptides / Q000493:pharmacokinetics; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D011817:Rabbits; D011877:Radionuclide Imaging; D018461:Soft Tissue Infections / Q000000981:diagnostic imaging*; D013203:Staphylococcal Infections / Q000000981:diagnostic imaging*; D013667:Technetium; D015054:Zymosan
D002630:Chemotactic Factors; D009842:Oligopeptides; D015609:Organotechnetium Compounds; C084664:technetium Tc 99m formyl-methionyl-leucyl-phenylalanyl-lysyl-hydrazinonicotinamide; C107636:technetium Tc 99m hydrazinonicotinamide-methionyl-leucyl-phenylalanine methyl ester; D009240:N-Formylmethionine Leucyl-Phenylalanine; C042932:formylmethionyl-leucyl-phenylalanine methyl ester; D013667:Technetium; C049813:N-formylmethionyl-leucyl-phenylalanyl-lysine; D015054:Zymosan