title: Tuftsin derivatives of FITC, Tb-DOTA or Gd-DOTA as potential macrophage-specific imaging biomarkers.
abstract: Fluorescein- and terbium-labelled tuftsin (Thr-Lys-Pro-Arg) and pentapeptide (Thr-Lys-Pro-Pro-Arg) were synthesized and their properties were evaluated in vitro by luminescence spectrometry and confocal microscopy as fluorescence probes to target macrophage cells in biological systems. An increase in fluorescence of macrophages incubated with varying concentrations of fluorescein isothiocyanate or Tb-DOTA-tuftsin/pentapeptide conjugates was observed in a concentration-dependent manner. Tb-DOTA-pentapeptide had a greater affinity to macrophages than Tb-DOTA-tuftsin. Lipopolysaccharide (LPS) stimulation strengthened the internalization of peptide conjugates by macrophages through the tuftsin receptor mechanism. Tb-DOTA-tuftsin/pentapeptide conjugates are likely to be a promising optical reagents as probes of the immune response with involvement of macrophage cells in a variety of diseases. Gd-DOTA-tuftsin conjugate was also evaluated as a cell-specific contrast agent in in vitro MRI experiments. In this context, the macrophages labelled by Gd-DOTA-tuftsin were highly magnetic and detectable by MRI, which confirms that this vectorized MRI probe has the potential to image macrophage-mediated inflammation in diseases like brain traumas and stroke. Tuftsin receptor-specific biological-function domain may have a modified in vivo biodistribution profile, bioavailability and pharmacokinetics subsequent to its conjugation to a metal ion-binding backbone.
authors.affiliation: State Key Laboratory of Magnetic Resonance and Molecular and Atomic Physics, Wuhan Institute of Physics and Mathematics, The Chinese Academy of Sciences, Wuhan 430071, China. jianghua.feng@hotmail.com
authors.forename: Jianghua
authors.initials: J
authors.lastname: Feng
authors.forename: Marco M
authors.initials: MM
authors.lastname: Meloni
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Allan
authors.forename: Stephen
authors.initials: S
authors.lastname: Faulkner
authors.forename: Johanna
authors.initials: J
authors.lastname: Narvainen
authors.forename: Rishma
authors.initials: R
authors.lastname: Vidyasagar
authors.forename: Risto
authors.initials: R
authors.lastname: Kauppinen
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000737:chemistry; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000737:chemistry*; D008264:Macrophages / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D009942:Organometallic Compounds / Q000737:chemistry*; D013725:Terbium / Q000737:chemistry*; D014018:Tissue Distribution; D014405:Tuftsin / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D015415:Biomarkers; D005456:Fluorescent Dyes; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D013725:Terbium; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate; D016650:Fluorescein-5-isothiocyanate; D014405:Tuftsin