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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 a 99mTc-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. Copyright © 2017 Elsevier B.V. All rights reserved.


Chrysoula-Evangelia Karachaliou, Charalampos Triantis, Christos Liolios, Lazaros Palamaris, Christos Zikos, Ourania E Tsitsilonis, Hubert Kalbacher, Wolfgang Voelter, George Loudos, Minas Papadopoulos, Ioannis Pirmettis, Evangelia Livaniou. In vivo biodistribution and imaging studies with a 99mTc-radiolabeled derivative of the C-terminus of prothymosin alpha in mice bearing experimentally-induced inflammation. European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. 2017 Apr;113:188-197

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PMID: 28087377

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