title: Detecting Chronic Post-Traumatic Osteomyelitis of Mouse Tibia via an IL-13Rα2 Targeted Metallofullerene Magnetic Resonance Imaging Probe.
abstract: Differential diagnosis of chronic post-traumatic osteomyelitis (CPO) from aseptic inflammation remains challenging, since both pathological processes share similar clinical symptoms. Here we utilized a novel targeted metallofullerene nanoparticle based magnetic resonance imaging (MRI) probe IL-13-TAMRA-Gd3N@C80(OH)30(CH2CH2COOH)20to detect CPO in mouse tibia via overexpressed IL-13Rα2 receptors. The functionalized metallofullerene was characterized by X-ray photoelectron spectroscopy. Upon lipopolysaccharide (LPS) stimulation, macrophage Raw 264.7 cells showed elevated IL-13Rα2 expression via immunofluorescence staining and increased MRI probe binding via built-in TAMRA fluorescence imaging. Trauma was induced in both tibia of mice and bacteria soaked suture was inserted into the right tibia to initiate infection. During the acute phase (1.5 weeks), luminol-bioluminescence imaging revealed much higher myeloperoxidase activity in the infected tibia compared to the sham. In the chronic phase (4 weeks), X-ray radiography illustrated bone deformation in the infected tibia compared to the sham. With T1weighted sequences, the probe clearly exhibited hyperintensity in the infection foci at both acute and chronic phases, which was not observed in the sham tibia. Histological analysis revealed severe bone structural destruction and massive inflammatory cell infiltration in the infected tibia. Immunohistochemistry confirmed abundant expression of IL-13Rα2 in the infection site. In summary, we developed a noninvasive imaging approach to detect and differentiate CPO from aseptic inflammation using a new IL-13Rα2 targeted metallofullerene MRI probe. In addition, for the first time, IL-13Rα2 was investigated as a unique biomarker in the context of osteomyelitis. Our data established a foundation for the translational application of this MRI probe in the clinical differentiation of CPO.
authors.forename: Li
authors.identifier: 0000-0003-1403-7472
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Department of Chemistry, Virginia Polytechnic Institute and State University , Blacksburg, Virginia 24061, United States.
authors.forename: Tinghui
authors.initials: T
authors.lastname: Li
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Ding
authors.forename: Jiezuan
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Chemistry, Virginia Polytechnic Institute and State University , Blacksburg, Virginia 24061, United States.
authors.forename: José
authors.initials: J
authors.lastname: Rodríguez-Corrales
authors.affiliation: Virginia Tech Carilion Research Institute , Roanoke, Virginia 24016, United States.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: LaConte
authors.forename: Nicholas
authors.initials: N
authors.lastname: Nacey
authors.forename: David B
authors.initials: DB
authors.lastname: Weiss
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.affiliation: Virginia Tech Carilion Research Institute , Roanoke, Virginia 24016, United States.|Department of Chemistry, Virginia Polytechnic Institute and State University , Blacksburg, Virginia 24061, United States.
authors.forename: Harry C
authors.initials: HC
authors.lastname: Dorn
authors.forename: Xudong
authors.initials: X
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015415:Biomarkers / Q000737:chemistry; D002908:Chronic Disease; D005260:Female; D037741:Fullerenes / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry*; D018793:Interleukin-13 / Q000737:chemistry*; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000032:analysis*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D053758:Nanoparticles / Q000737:chemistry; D010019:Osteomyelitis / Q000000981:diagnostic imaging*; D000067996:RAW 264.7 Cells; D053660:Receptors, Interleukin-13; D013977:Tibia / Q000000981:diagnostic imaging*
chemical_list: D015415:Biomarkers; D037741:Fullerenes; D018793:Interleukin-13; D053663:Interleukin-13 Receptor alpha2 Subunit; D053660:Receptors, Interleukin-13; D005682:Gadolinium