Inflammatory Response Assessed With An MPO-activatable Mn(Ⅱ)MR Probe In An Experimental Model Of Acute Gout

Objectives:With myeloperoxidase(MPO)as an imaging biomarker and a potential therapeutic target to evaluate the change of inflammatory response in animal models of acute goutusing the MPO-activatable Mn(Ⅱ)MR probe.Methods:Monosodium urate(MSU)crystal-induced mouse model of acute gouty on the left hind limbwas imaged with MPO-Mn and compared to Gd-DTPA and Mn-EDTA.With 4-aminobenzoic acid hydrazide(ABAH)as the inhibitor of MPO,the imaging characteristic of the inflammatory response was dynamically tracked with MPO-Mn.The progression of the inflammatory response was further evaluated by MPO enzyme activity assays,western blotting,and histology analyses and corroborated with imaging results.All data were compared with student t-test.Results:1.MR imaging studies were performed after intravenous administration of MPO-Mn,Gd-DTPA and Mn-EDTA.①Compared to Gd-DTPA,MPO-Mn can produce 1.62-fold ΔCNR than Gd-DTPA(post-injection 14 minutes,22.54±1.86 vs 13.90±2.22,P<0.001).②Compared to Mn-EDTA,the signal intensity produced by MPO-Mn was significantly better than that of Mn-EDTA,and there was a difference inΔCNR between two contrast agents at 2 minutes(15.68 ± 1.92 vs 10.39 ±3.27,P=0.003)and then this difference gradually increased.However,On the right hind limb(as a control group),there were no significant differences in the normalized signal-to-noise ratio(nSNR)produced by three contrast agents.2.Compared to the saline group,MPO-Mn MR imaging study of the ABAH group showed a significantly lower ΔCNR on the diseased hind limb at 6 minutes(22.96 ± 3.12vs 17.81±1.58,P=0.011)and then continued to decrease until 30 minutes.In addition,the reduction of lesion volume(1.14±0.15 mm3/gvs0.55 ± 0.16 mm3/g,P<0.001),MPO enzyme activity(1.12 ±0.07 U/mgvs 0.75±0.12 U/mg,P<0.001),MPO protein relative expression(1.48±0.19vs0.98±0.09,P<0.001)and inflammatory cell recruitment.Conclusions:MPO might be an imaging biomarker,the inflammatory lesions of acute gout animal models may be located by MPO-Mn.With MPO as a therapeutic target,ABAH to improve the prognosis of acute goutmay be detected and assessed in vivo by MPO-Mn.