Ga-68-WRWWWW Is a Potential Positron Emission Tomography Probe for Imaging Inflammatory Diseases by Targeting Formyl Peptide Receptor 2

Inflammation plays a significant role in many physiological and pathologicalprocesses. Molecular imaging could provide functional as well as anatomical information forvisualizing various inflammatory diseases. Advancements in imaging tracers for inflammationwould improve the accuracy of diagnosis and monitoring, thus facilitating patient care. Thepositron emission tomography (PET) imaging tracer,68Ga-labeled antagonist peptide Trp-Arg-Trp-Trp-Trp-Trp (WRWWWW, WRW4), targets formyl peptide receptor 2 (FPR2), which isin turn widely distributed in a variety of tissues and is associated with many inflammatorydiseases. In the current study, we aimed to investigate the potential of68Ga-WRW4fordetecting and monitoring inflammatory lesions in mice. We established an inflammation mousemodel by the intramuscular injection of turpentine oil into the left thigh. WRW4was labeledwith68Ga with an overall radiochemical yield >90% and radiochemical purity >99%.68Ga-WRW4uptake in inflamed muscle peaked on day 2 (1.14 +/- 0.01 percentage of the injecteddose per gram of tissue (%ID/g)) and the uptake ratio of inflammatory/normal muscle alsoreached a maximum (12.36 +/- 2.35). Strong PET signals were detected in the left thigh at 60min after the injection of68Ga-WRW4in experimental mice, but weak or no signals were detected in mice in the blocking andcontrol groups.68Ga-WRW4uptake was in agreement with the dynamics of immune cell infiltration during the inflammatoryreaction. These results suggest that68Ga-WRW4is a promising PET tracer suitable for the noninvasive detection of FPR2 expressionand for monitoring inflammatory activity in inflammation-bearing mice.