Abstract
Within the last years Zr has attracted increasing attention as long lived PET radionuclide. So far the bifunctional chelating system employed for Zr-applications is desferrioxamine B (DFO). Fusarinine C (FSC), a cyclic peptide siderophore, could be an alternative with potentially higher stability due to its cyclic structure, having complexing properties comparable to DFO. As proof of principle in this study Zr-labelling of RGD-derivatised FSC, the optimization of analytical procedures and preliminary evaluation of this compound are reported. High radiochemical yield (N96%) for Zr-FSC-(RGD)3 could be achieved at high SA. HPLC was used for characterization of Zr-FSC(RGD)3, but was not suitable for determination of RCP. Using TLC best separation properties were achieved using ITLC-SG and CH3COOH/H2O (1:9) as a mobile phase. In vitro characterization of [Zr]FSC-(RGD)3 showed comparable properties to the Ga-counterpart with a hydrophilic character (logD value of −2.9) and low serum protein-bound activity. [Zr]FSC-(RGD)3 was stable in PBS (pH 7.4), in FeCl3-solution as well as in fresh human serum, in DTPAsolution at 37 °C at 24 hours a slight degradation of the Zr-peptide was found. Cell internalized activity was 2.07% cpm/mg protein for αvβ3 positive M21 cells which could be reduced to 0.23% cpm/mg protein via addition of c(RGDyV) revealing specific receptor binding. These results indicate very promising properties of the fusarinine C scaffold as basis for multimeric targeting constructs for labelling with Zr. Biodistribution experiments are currently ongoing.
Published Version
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