Synthesis, Radiolabelling and In Vitro Characterization of the Gallium-68-, Yttrium-90- and Lutetium-177-Labelled PSMA Ligand, CHX-A''-DTPA-DUPA-Pep

• Main Authors: Benjamin Baur, Christoph Solbach, Elena Andreolli, Gordon Winter, Hans-Jürgen Machulla, Sven N. Reske
• Format: Article
• Language: English
• Published: MDPI AG 2014-04-01
• Series: Pharmaceuticals
• Subjects: PSMA; prostate-specific membrane antigen; PET; positron emission tomography; prostate cancer; DUPA; Ga-68; Y-90; Lu-177; radionuclide therapy
• Online Access: http://www.mdpi.com/1424-8247/7/5/517

Since prostate-specific membrane antigen (PSMA) has been identified as a diagnostic target for prostate cancer, many urea-based small PSMA-targeting molecules were developed. First, the clinical application of these Ga-68 labelled compounds in positron emission tomography (PET) showed their diagnostic potential. Besides, the therapy of prostate cancer is a demanding field, and the use of radiometals with PSMA bearing ligands is a valid approach. In this work, we describe the synthesis of a new PSMA ligand, CHX-A''-DTPA-DUPA-Pep, the subsequent labelling with Ga-68, Lu-177 and Y-90 and the first in vitro characterization. In cell investigations with PSMA-positive LNCaP C4-2 cells, KD values of ≤14.67 ± 1.95 nM were determined, indicating high biological activities towards PSMA. Radiosyntheses with Ga-68, Lu-177 and Y-90 were developed under mild reaction conditions (room temperature, moderate pH of 5.5 and 7.4, respectively) and resulted in nearly quantitative radiochemical yields within 5 min.