Tc-99m-labeled C5a and C5a des Arg74 for infection imaging.
The complement anaphylatoxin C5a and its natural metabolite C5a des Arg(74) (C5adR) are involved in several stages of the inflammatory process. Both act on a common receptor expressed on different cell types, including neutrophils and monocytes. The receptor binding affinity of C5a is in the nanomolar range and exceeds that of C5adR by 1-2 orders of magnitude. The biologic potency of C5a is considerably higher than that of C5adR. Here we tested both proteins labeled with (99m)Tc for imaging of infection.


METHODS
The proteins were labeled with (99m)Tc via the hydrazinonicotinamide (HYNIC) chelator. The preparations were tested for imaging of infection in a rabbit model of intramuscular infection. Biodistribution of the radiolabel was determined by gamma-camera imaging and by counting dissected tissues at 5 h p.i.


RESULTS
C5a and C5adR showed in vivo abscess uptakes of 0.12 and 0.025%ID/g, abscess/muscle ratios of 76 and 14, abscess/blood ratios of 9.1 and 2.6, and ROI derived target-to-background ratios of 5.9 and 2.1, respectively at 5 h p.i.


CONCLUSIONS
For infection imaging (99m)Tc-labeled C5a showed excellent in vivo characteristics. However, C5a is a very bioactive protein, impeding its clinical use as an infection imaging agent. The naturally occurring partial agonist C5adR has less biological effect but showed suboptimal imaging characteristics. The present study showed that for adequate localization of a receptor binding ligand affinities for the receptor in the nanomolar range are required.
Rennen
H J
HJ
University Medical Center Nijmegen, Nijmegen, The Netherlands. H.Rennen@nucmed.umcn.nl
Oyen
W J
WJ
Cain
S A
SA
Monk
P N
PN
Corstens
F H
FH
Boerman
O C
OC
D000818:Animals; D017304:Annexin A5 / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007239:Infections / Q000000981:diagnostic imaging; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D011817:Rabbits; D011877:Radionuclide Imaging; D014018:Tissue Distribution
D017304:Annexin A5; D015609:Organotechnetium Compounds; C117287:technetium Tc 99m HYNIC annexin V