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A receptor-specific peptide for imaging infection and inflammation
P S Rao1, V R Pallela, D Vassileva-Belnikolovska
1Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA.
Abstract:
The chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (fMLP), when radiolabelled, continues to be an attractive agent for imaging infection or inflammation. Previously, several analogues of fMLP have been prepared and radiolabelled using a bifunctional chelating agent conjugation procedure that was relatively long and complex. We have prepared a new analogue of fMLP, TP765, by the addition of 4-aminobutyric acid (4-ABA) and a group of four amino acids, Gly-Gly-d-Ala-Gly, to the carboxy terminus (i.e. to the phenylalanine) of fMLP. The adduct -(4-ABA)-Gly-Gly-d-Ala-Gly- serves as a chelating moiety for strong chelation with 99Tcm. The use of a peptide as a chelating moiety greatly simplified the synthetic procedure and rendered the analogue ready for instant chelation with 99Tcm. HPLC analysis revealed that 99Tcm-TP765 was a single chemical entity that retained biological activity and neutrophil specificity. 99Tcm-TP765 was stable when challenged with strong chelating agents in vitro and had rapid but biphasic blood clearance (alphat1/2 = 7 min, betat1/2 = 45 min). Approximately 90% of the radioactivity had cleared from circulation within 45 min post-injection and the agent had accumulated in experimental bacterial or sterile abscesses in significantly (P<0.05) higher quantities than the analogues evaluated previously. Generally, the biodistribution pattern of 99Tcm-TP765 was similar to that of other analogues examined and its abscess uptake was independent of the abscess age. In conclusion, a new analogue of fMLP, 99Tcm-TP765, was prepared by a simple procedure. This new analogue has properties similar to those of previously examined analogues used as agents for imaging infection or inflammation.
Insights
A new radiolabeled N-formylmethionyl-leucyl-phenylalanine (fMLP) analogue, 99Tcm-TP765, simplifies infection imaging. This agent shows high specificity and abscess uptake, offering improved diagnostic potential.
Area of Science:
- Nuclear medicine
- Radiopharmaceutical chemistry
- Molecular imaging
Background:
- N-formylmethionyl-leucyl-phenylalanine (fMLP) analogues are used for infection and inflammation imaging.
- Previous radiolabeling methods for fMLP analogues were complex and time-consuming.
Purpose of the Study:
- To develop a novel, simplified method for preparing radiolabeled fMLP analogues for infection imaging.
- To evaluate the properties and efficacy of the new analogue, 99Tcm-TP765.
Main Methods:
- A new fMLP analogue, TP765, was synthesized by adding 4-aminobutyric acid and a peptide sequence to fMLP's carboxy terminus.
- The peptide sequence served as a chelating moiety for technetium-99m (99Tcm) labeling.
- High-performance liquid chromatography (HPLC) was used to confirm purity and biological activity.
Main Results:
- 99Tcm-TP765 was prepared via a simplified procedure, allowing instant chelation with 99Tcm.
- HPLC confirmed 99Tcm-TP765 as a single entity with retained biological activity and neutrophil specificity.
- The agent exhibited rapid, biphasic blood clearance and significant accumulation in experimental abscesses, outperforming previous analogues.
Conclusions:
- A novel fMLP analogue, 99Tcm-TP765, was successfully synthesized using a straightforward method.
- 99Tcm-TP765 demonstrates favorable characteristics for infection and inflammation imaging, including stability, specificity, and enhanced abscess uptake.
