Identification, Characterization, and Suppression of Side Products Formed during the Synthesis of [<sup>177</sup>Lu]Lu-PSMA-617.
Détails
ID Serval
serval:BIB_A46AADF303C9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Identification, Characterization, and Suppression of Side Products Formed during the Synthesis of [<sup>177</sup>Lu]Lu-PSMA-617.
Périodique
Journal of medicinal chemistry
ISSN
1520-4804 (Electronic)
ISSN-L
0022-2623
Statut éditorial
Publié
Date de publication
22/04/2021
Peer-reviewed
Oui
Volume
64
Numéro
8
Pages
4960-4971
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
In recent years, radiolabeled tracers targeting prostate-specific membrane antigen (PSMA) have had a tremendous impact on prostate cancer management. Here, we report on the formation of radioactive impurities formed during the clinical production of <sup>177</sup> Lu-labeled PSMA-617. We provide compelling evidence that these impurities are the result of a spontaneous, thermally mediated condensation reaction of the Glu-CO-Lys moiety resulting in the formation of three different five-membered ring systems. Density functional theory (DFT) calculations show that the condensation and cyclization of the Glu-CO-Lys moiety is thermodynamically spontaneous. In cell experiments, no affinity of these cyclized compounds toward PSMA was observed. HPLC analyses of urine samples from patient studies showed rapid renal excretion of these radioactive cyclized species. Radiolabeling conditions were identified that significantly reduced the formation of cyclized side products yielding <sup>177</sup> Lu-labeled PSMA-617 in high radiochemical yield and purity in concordance with current good manufacturing practice (cGMP) requirements.
Pubmed
Web of science
Création de la notice
12/04/2021 12:02
Dernière modification de la notice
16/12/2021 7:32