title: In vivo biodistribution and imaging studies with a99mTc-radiolabeled derivative of the C-terminus of prothymosin alpha in mice bearing experimentally-induced inflammation.
abstract: Prothymosin alpha (ProTα) is a highly conserved mammalian polypeptide (109 amino acids in man) exerting in vitro and in vivo immunoenhancing activities. Recently, our team has developed a99mTc-radiolabeled derivative of the C-terminal bioactive decapeptide of ProTα ([99mTc]C1) and employed it in in vitro studies, the results of which support the existence of binding sites on human neutrophils that recognize [99mTc]C1, intact ProTα as well as the C-terminal decapeptide of ProTα and presumably involve Toll-like receptor 4. In the present work, [99mTc]C1 was administered to Swiss albino mice with experimentally-induced inflammation for in vivo biodistribution and imaging studies, in parallel with a suitable negative control, which differs from [99mTc]C1 only in bearing a scrambled version of the ProTα decapeptide. The biodistribution data obtained with [99mTc]C1 demonstrated fast clearance of radioactivity from blood, heart, lungs, normal muscle, and predominantly urinary excretion. Most importantly, slow clearance of radioactivity from the inflammation focus was observed, resulting in a high ratio of inflamed/normal muscle tissue (9.15 at 30min post injection, which remained practically stable up to 2h). The inflammation-targeting capacity of [99mTc]C1 was confirmed by imaging studies and might be attributed to neutrophils, which are recruited at the inflamed areas and bear binding sites for [99mTc]C1. In this respect, apart from being a valuable tool for further studies on ProTα in in vitro and in vivo systems, [99mTc]C1 merits further evaluation as a radiopharmaceutical for specific imaging of inflammation foci.
authors.affiliation: Institute of Nuclear and Radiological Sciences and Technology, Energy and Safety (INRASTES), National Center for Scientific Research "Demokritos" (NCSR "Demokritos"), Athens 15310, Greece.
authors.forename: Chrysoula-Evangelia
authors.initials: CE
authors.lastname: Karachaliou
authors.affiliation: Institute of Nuclear and Radiological Sciences and Technology, Energy and Safety (INRASTES), National Center for Scientific Research "Demokritos" (NCSR "Demokritos"), Athens 15310, Greece.
authors.forename: Charalampos
authors.initials: C
authors.lastname: Triantis
authors.affiliation: Institute of Nuclear and Radiological Sciences and Technology, Energy and Safety (INRASTES), National Center for Scientific Research "Demokritos" (NCSR "Demokritos"), Athens 15310, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Liolios
authors.affiliation: Department of Medical Instruments Technology, Technological Educational Institute, Athens 12243, Greece.
authors.forename: Lazaros
authors.initials: L
authors.lastname: Palamaris
authors.affiliation: Institute of Nuclear and Radiological Sciences and Technology, Energy and Safety (INRASTES), National Center for Scientific Research "Demokritos" (NCSR "Demokritos"), Athens 15310, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Zikos
authors.affiliation: Division of Animal and Human Physiology, Department of Biology, University of Athens, Athens 15784, Greece.
authors.forename: Ourania E
authors.initials: OE
authors.lastname: Tsitsilonis
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tuebingen, Tuebingen 72076, Germany.
authors.forename: Hubert
authors.initials: H
authors.lastname: Kalbacher
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tuebingen, Tuebingen 72076, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Voelter
authors.affiliation: Department of Medical Instruments Technology, Technological Educational Institute, Athens 12243, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Loudos
authors.affiliation: Institute of Nuclear and Radiological Sciences and Technology, Energy and Safety (INRASTES), National Center for Scientific Research "Demokritos" (NCSR "Demokritos"), Athens 15310, Greece.
authors.forename: Minas
authors.initials: M
authors.lastname: Papadopoulos
authors.affiliation: Institute of Nuclear and Radiological Sciences and Technology, Energy and Safety (INRASTES), National Center for Scientific Research "Demokritos" (NCSR "Demokritos"), Athens 15310, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Pirmettis
authors.affiliation: Institute of Nuclear and Radiological Sciences and Technology, Energy and Safety (INRASTES), National Center for Scientific Research "Demokritos" (NCSR "Demokritos"), Athens 15310, Greece. Electronic address: livanlts@rrp.demokritos.gr.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Livaniou
mesh_terms: D000818:Animals; D006801:Humans; D007249:Inflammation / Q000000981:diagnostic imaging / Q000378:metabolism*; D051379:Mice; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D011498:Protein Precursors / Q000378:metabolism*; D013947:Thymosin / Q000031:analogs & derivatives* / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D015609:Organotechnetium Compounds; D011498:Protein Precursors; C040782:prothymosin alpha; D013947:Thymosin
keywords: (99m)Tc-radiolabeled derivative of ProTα ([(99m)Tc]C1); C-terminal decapeptide of ProTα (ProTα[100–109]); In vivo biodistribution studies; In vivo imaging; Inflammation; Prothymosin alpha (ProTα)