Novel Bifunctional Cyclic Chelator for (89)Zr Labeling-Radiolabeling and Targeting Properties of RGD Conjugates.
Within the last years (89)Zr has attracted considerable attention as long-lived radionuclide for positron emission tomography (PET) applications. So far desferrioxamine B (DFO) has been mainly used as bifunctional chelating system. Fusarinine C (FSC), having complexing properties comparable to DFO, was expected to be an alternative with potentially higher stability due to its cyclic structure. In this study, as proof of principle, various FSC-RGD conjugates targeting αvß3 integrins were synthesized using different conjugation strategies and labeled with (89)Zr. In vitro stability, biodistribution, and microPET/CT imaging were evaluated using [(89)Zr]FSC-RGD conjugates or [(89)Zr]triacetylfusarinine C (TAFC). Quantitative (89)Zr labeling was achieved within 90 min at room temperature. The distribution coefficients of the different radioligands indicate hydrophilic character. Compared to [(89)Zr]DFO, [(89)Zr]FSC derivatives showed excellent in vitro stability and resistance against transchelation in phosphate buffered saline (PBS), ethylenediaminetetraacetic acid solution (EDTA), and human serum for up to 7 days. Cell binding studies and biodistribution as well as microPET/CT imaging experiments showed efficient receptor-specific targeting of [(89)Zr]FSC-RGD conjugates. No bone uptake was observed analyzing PET images indicating high in vivo stability. These findings indicate that FSC is a highly promising chelator for the development of (89)Zr-based PET imaging agents.
†Department of Nuclear Medicine, Medical University Innsbruck, Innsbruck, Austria.
Chuangyan
C
Zhai
†Department of Nuclear Medicine, Medical University Innsbruck, Innsbruck, Austria.
Dominik
D
Summer
†Department of Nuclear Medicine, Medical University Innsbruck, Innsbruck, Austria.
Christine
C
Rangger
Gerben M
GM
Franssen
Peter
P
Laverman
§Division of Molecular Biology, Medical University Innsbruck, Innsbruck, Austria.
Hubertus
H
Haas
∥Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
Milos
M
Petrik
†Department of Nuclear Medicine, Medical University Innsbruck, Innsbruck, Austria.
Roland
R
Haubner
†Department of Nuclear Medicine, Medical University Innsbruck, Innsbruck, Austria.
Clemens
C
Decristoforo
D002614:Chelating Agents / Q000737:chemistry*; D005290:Ferric Compounds / Q000737:chemistry; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry; D049268:Positron-Emission Tomography; D011868:Radioisotopes / Q000737:chemistry*; D015040:Zirconium / Q000737:chemistry
D002614:Chelating Agents; D005290:Ferric Compounds; D006877:Hydroxamic Acids; D009842:Oligopeptides; D011868:Radioisotopes; C010966:fusigen; C053324:N,N',N''-triacetylfusarinine C; C047981:arginyl-glycyl-aspartic acid; D015040:Zirconium
89Zr; RGD peptide; fusarinine C; positron emission tomography (PET); triacetylfusarinine C