Identification, Characterization, and Suppression of Side Products Formed during the Synthesis of [<sup>177</sup>Lu]Lu-PSMA-617.

Details

Serval ID
serval:BIB_A46AADF303C9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Identification, Characterization, and Suppression of Side Products Formed during the Synthesis of [<sup>177</sup>Lu]Lu-PSMA-617.
Journal
Journal of medicinal chemistry
Author(s)
Martin S., Tönnesmann R., Hierlmeier I., Maus S., Rosar F., Ruf J., Holland J.P., Ezziddin S., Bartholomä M.D.
ISSN
1520-4804 (Electronic)
ISSN-L
0022-2623
Publication state
Published
Issued date
22/04/2021
Peer-reviewed
Oui
Volume
64
Number
8
Pages
4960-4971
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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
Create date
12/04/2021 11:02
Last modification date
16/12/2021 6:32
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