UNLABELLED: 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.
UNLABELLED: 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.
Authors: Tamara Boltersdorf; Junaid Ansari; Elena Y Senchenkova; Jieny Groeper; Denise Pajonczyk; Shantel A Vital; Gaganpreet Kaur; J Steve Alexander; Thomas Vogl; Ursula Rescher; Nicholas J Long; Felicity N E Gavins Journal: Theranostics Date: 2020-05-17 Impact factor: 11.556
Authors: Landon W Locke; Mahendra D Chordia; Yi Zhang; Bijoy Kundu; Dylan Kennedy; Jessica Landseadel; Li Xiao; Karen D Fairchild; Stuart S Berr; Joel Linden; Dongfeng Pan Journal: J Nucl Med Date: 2009-04-16 Impact factor: 10.057