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.

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 30 min post injection, which remained practically stable up to 2 h). 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.