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Tc-99m-labeled C5a and C5a des Arg74 for infection imaging
H J Rennen1, W J Oyen, S A Cain
1University Medical Center Nijmegen, Nijmegen, The Netherlands. H.Rennen@nucmed.umcn.nl
Nuclear Medicine and Biology
|May 15, 2003
Summary
Technetium-99m-labeled complement anaphylatoxin C5a (C5a) demonstrated excellent in vivo characteristics for infection imaging. However, its high bioactivity limits clinical use, while C5a des Arg(74) (C5adR) showed suboptimal imaging, highlighting the need for nanomolar receptor binding affinity.
Area of Science:
- Biochemistry
- Immunology
- Radiochemistry
Background:
- Complement anaphylatoxin C5a and its metabolite C5a des Arg(74) (C5adR) are key players in inflammation.
- Both C5a and C5adR bind to the same receptor on neutrophils and monocytes.
- C5a exhibits significantly higher receptor binding affinity and biological potency than C5adR.
Purpose of the Study:
- To evaluate the potential of (99m)Tc-labeled C5a and C5adR as imaging agents for infection.
- To compare the in vivo imaging characteristics of C5a and C5adR.
Main Methods:
- Proteins C5a and C5adR were labeled with (99m)Tc using the HYNIC chelator.
- Infection imaging was performed in a rabbit intramuscular infection model.
- Biodistribution and imaging were assessed using gamma-camera imaging and tissue counting at 5 hours post-infection.
Main Results:
- (99m)Tc-labeled C5a showed higher abscess uptake (0.12%ID/g) and better target-to-background ratios (76:1 abscess/muscle, 9.1:1 abscess/blood) compared to C5adR (0.025%ID/g, 14:1, 2.6:1).
- C5a demonstrated excellent in vivo characteristics for infection imaging.
- C5adR exhibited suboptimal imaging performance.
Conclusions:
- (99m)Tc-labeled C5a is a promising agent for infection imaging due to its excellent in vivo characteristics.
- The high bioactivity of C5a may impede its clinical application.
- Effective receptor-binding ligand localization for imaging requires nanomolar receptor affinities, as demonstrated by the suboptimal performance of C5adR.
