1. In vivo biodistribution and imaging studies with a 99m Tc-radiolabeled derivative of the C-terminus of prothymosin alpha in mice bearing experimentally-induced inflammation.
- Author
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Karachaliou CE, Triantis C, Liolios C, Palamaris L, Zikos C, Tsitsilonis OE, Kalbacher H, Voelter W, Loudos G, Papadopoulos M, Pirmettis I, and Livaniou E
- Subjects
- Animals, Humans, Inflammation diagnostic imaging, Mice, Thymosin metabolism, Tissue Distribution, Inflammation metabolism, Organotechnetium Compounds pharmacokinetics, Protein Precursors metabolism, Thymosin analogs & derivatives
- 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 a
99m Tc-radiolabeled derivative of the C-terminal bioactive decapeptide of ProTα ([99m Tc]C1) and employed it in in vitro studies, the results of which support the existence of binding sites on human neutrophils that recognize [99m Tc]C1, intact ProTα as well as the C-terminal decapeptide of ProTα and presumably involve Toll-like receptor 4. In the present work, [99m Tc]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 [99m Tc]C1 only in bearing a scrambled version of the ProTα decapeptide. The biodistribution data obtained with [99m Tc]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 [99m Tc]C1 was confirmed by imaging studies and might be attributed to neutrophils, which are recruited at the inflamed areas and bear binding sites for [99m Tc]C1. In this respect, apart from being a valuable tool for further studies on ProTα in in vitro and in vivo systems, [99m Tc]C1 merits further evaluation as a radiopharmaceutical for specific imaging of inflammation foci., (Copyright © 2017 Elsevier B.V. All rights reserved.)- Published
- 2017
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