Preclinical Evaluation of Gastrin-Releasing Peptide Receptor Antagonists Labeled with 161 Tb and 177 Lu: A Comparative Study.

Autor: Holzleitner N; Department of Chemistry, School of Natural Sciences, Technical University of Munich, Garching, Germany., Cwojdzinski T; Department of Chemistry, School of Natural Sciences, Technical University of Munich, Garching, Germany., Beck R; Department of Chemistry, School of Natural Sciences, Technical University of Munich, Garching, Germany., Urtz-Urban N; Department of Chemistry, School of Natural Sciences, Technical University of Munich, Garching, Germany., Hillhouse CC; Center for Radiopharmaceutical Sciences ETH-PSI, Paul Scherrer Institute, Villigen, Switzerland; and., Grundler PV; Center for Radiopharmaceutical Sciences ETH-PSI, Paul Scherrer Institute, Villigen, Switzerland; and., van der Meulen NP; Center for Radiopharmaceutical Sciences ETH-PSI, Paul Scherrer Institute, Villigen, Switzerland; and., Talip Z; Center for Radiopharmaceutical Sciences ETH-PSI, Paul Scherrer Institute, Villigen, Switzerland; and., Ramaekers S; Nuclear Medical Applications, Belgian Nuclear Research Centre, Mol, Belgium., Van de Voorde M; Nuclear Medical Applications, Belgian Nuclear Research Centre, Mol, Belgium., Ponsard B; Nuclear Medical Applications, Belgian Nuclear Research Centre, Mol, Belgium., Casini A; Department of Chemistry, School of Natural Sciences, Technical University of Munich, Garching, Germany; thomas.guenther@tum.de angela.casini@tum.de., Günther T; Department of Chemistry, School of Natural Sciences, Technical University of Munich, Garching, Germany; thomas.guenther@tum.de angela.casini@tum.de.
Jazyk: angličtina
Zdroj: Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2024 Mar 01; Vol. 65 (3), pp. 481-484. Date of Electronic Publication: 2024 Mar 01.
DOI: 10.2967/jnumed.123.266233
Abstrakt: To elucidate potential benefits of the Auger-electron-emitting radionuclide 161 Tb, we compared the preclinical performance of the gastrin-releasing peptide receptor antagonists RM2 (DOTA-Pip 5 -d-Phe 6 -Gln 7 -Trp 8 -Ala 9 -Val 10 -Gly 11 -His 12 -Sta 13 -Leu 14 -NH 2 ) and AMTG (α-Me-Trp 8 -RM2), each labeled with both 177 Lu and 161 Tb. Methods: 161 Tb/ 177 Lu labeling (90°C, 5 min) and cell-based experiments (PC-3 cells) were performed. In vivo stability (30 min after injection) and biodistribution studies (1-72 h after injection) were performed on PC-3 tumor-bearing CB17-SCID mice. Results: Gastrin-releasing peptide receptor affinity was high for all compounds (half-maximal inhibitory concentration [nM]: [ 161 Tb]Tb-RM2, 2.46 ± 0.16; [ 161 Tb]Tb-AMTG, 2.16 ± 0.09; [ 177 Lu]Lu-RM2, 3.45 ± 0.18; [ 177 Lu]Lu-AMTG, 3.04 ± 0.08), and 75%-84% of cell-associated activity was receptor-bound. In vivo, both AMTG analogs displayed distinctly higher stability (30 min after injection) and noticeably higher tumor retention than their RM2 counterparts. Conclusion: On the basis of preclinical results, [ 161 Tb]Tb-/[ 177 Lu]Lu-AMTG might reveal a higher therapeutic efficacy than [ 161 Tb]Tb-/[ 177 Lu]Lu-RM2, particularly [ 161 Tb]Tb-AMTG because of additional Auger-electron emissions at the cell membrane level.
(© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)
Databáze: MEDLINE
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