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

Pharmaceuticals

Benjamin Baur¹  Christoph Solbach¹  Elena Andreolli¹  Gordon Winter¹  Hans-Jürgen Machulla¹ 

[1] Clinic for Nuclear Medicine, University of Ulm, Albert-Einstein-Allee, 89081 Ulm, Germany; E-Mails:

关键词: PSMA;    prostate-specific membrane antigen;    PET;    positron emission tomography;    prostate cancer;    DUPA;    Ga-68;    Y-90;    Lu-177;    radionuclide therapy;   

DOI  :  10.3390/ph7050517

来源: mdpi

【 摘 要 】

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, K_D 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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.