| Affiliation: | 1. Institute of Nuclear Chemistry, Johannes Gutenberg University, Fritz-Strassmann-Weg 2, 55128 Mainz, Germany;2. Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden Rossendorf, Bautzner Landstraße 400, 01328 Dresden, Germany
Department of Biophysics and Radiation Biology, Semmelweis University, T?zoltó u. 37–47, 1094 Budapest, Hungary;3. Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden Rossendorf, Bautzner Landstraße 400, 01328 Dresden, Germany |
| Abstract: | The L-lysine urea-L-glutamate (KuE) represents a key motif in recent diagnostic and therapeutic radiopharmaceuticals targeting the prostate specific membrane antigen (PSMA). Using a squaric acid moiety for coupling of KuE with a radioactive label, the squaric acid as a linker in the PSMA ligand seems to mimic the aromatic structure of the naphthylalanine unit on PSMA-617. In this work, we investigate the influence of squaric acid moiety on the biological activity of the compound carrying a KuE motif and three typical chelates. The derivatives TRAM.SA.KuE, DOTAGA.SA.KuE and NODAGA.SA.KuE were all synthesized in straightforward organic reactions and purified by HPLC afterward. Different amounts of tracer were labeled at different temperatures with 68Ga. PET examinations were performed on NMRInu/nu nude mice with an LNCaP tumor on the right hind leg including ex vivo investigations of the organs. For comparison, 68Ga-derivatives of PSMA-11 and PSMA-617, the derivatives most commonly used in clinics, were investigated in the same animal model. |
