title: Radiofluorination of PSMA-HBED via Al(18)F(2+) Chelation and Biological Evaluations In Vitro.
abstract: OBJECTIVE
  Ga-68-labeled prostate-specific membrane antigen (PSMA) ligands have been used clinically for positron emission tomography (PET) imaging of prostate cancer. However, F-18-labeled compounds offer several advantages, including the potential for delayed imaging, high starting activities enabling multidose preparation, and improved spatial resolution in PET. For F-18 labeling of peptides conjugated with a suitable chelator, a fast and feasible method is the use of [Al(18)F](2+). In the present study, the radiofluorinations of a well-known PSMA ligand Glu-NH-CO-NH-Lys(Ahx)-HBED-CC (PSMA-HBED) via [Al(18)F](2+) were performed with respect to various reaction parameters, along with the biological evaluations in a cell experiment.
  
  
  METHODS
  [Al(18)F]PSMA-HBED was prepared by adding Na[(18)F]F into a vial containing 0.026 μmol peptide (in 0.05 M NaOAc buffer) and 0.03 μmol AlCl3⋅6H2O (in 0.05 M NaOAc buffer). Then, it was stirred at different temperatures from 1 to 30 min. Afterwards, purification was carried out by solid phase extraction. Biological evaluations were performed in PSMA-positive cell lines LNCaP C4-2, along with a negative control using PC-3 cell lines.
  
  
  RESULTS
  The best labeling results (81 ± 0.5 %, n = 4) were observed with 0.026 μmol peptide (30 °C, 5 min). For preclinical experiments, the production of [Al(18)F]PSMA-HBED at 35 °C including purification by solid phase extraction (SPE) succeeded within 45 min, resulting in a radiochemical yield of 49 ± 1.2 % (decay-corrected, n = 6, radiochemical purity ≥98 %) at EOS. The labeled peptide revealed serum stability for 4 h as well as a promising binding coefficient (K D) value of 10.3 ± 2.2 nM in cell experiments with PSMA-positive LNCaP C4-2 cells.
  
  
  CONCLUSIONS
  An efficient and one-pot method for the radiosynthesis of [Al(18)F]PSMA-HBED was developed (0.26 μmol of precursor at 35 °C). In cell culture studies, the K D suggests [Al(18)F]PSMA-HBED as a potential PSMA ligand for future investigations in vivo and clinical applications afterwards.
authors: Clinic for Nuclear Medicine, University Hospital Ulm, Ulm, Germany. noeen.malik@uniklinik-ulm.de.
authors: Noeen
authors: N
authors: Malik
authors: Clinic for Nuclear Medicine, University Hospital Ulm, Ulm, Germany.
authors: Benjamin
authors: B
authors: Baur
authors: Clinic for Nuclear Medicine, University Hospital Ulm, Ulm, Germany.
authors: Gordon
authors: G
authors: Winter
authors: Clinic for Nuclear Medicine, University Hospital Ulm, Ulm, Germany.
authors: Sven N
authors: SN
authors: Reske
authors: Clinic for Nuclear Medicine, University Hospital Ulm, Ulm, Germany.
authors: Ambros J
authors: AJ
authors: Beer
authors: Clinic for Nuclear Medicine, University Hospital Ulm, Ulm, Germany.
authors: Christoph
authors: C
authors: Solbach
mesh_terms: D000954:Antigens, Surface / Q000737:chemistry*; D002614:Chelating Agents / Q000737:chemistry*; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D043425:Glutamate Carboxypeptidase II / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018796:Immunoconjugates / Q000008:administration & dosage* / Q000737:chemistry*; D066298:In Vitro Techniques
chemical_list: D000954:Antigens, Surface; D002614:Chelating Agents; D005462:Fluorine Radioisotopes; D018796:Immunoconjugates; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II
keywords: Al18F-labeling; F-18; PSMA; PSMA-HBED; Prostate cancer