PT  - JOURNAL ARTICLE
AU  - Holzleitner, Nadine
AU  - Cwojdzinski, Tatjana
AU  - Beck, Roswitha
AU  - Urtz-Urban, Nicole
AU  - Hillhouse, Colin C.
AU  - Grundler, Pascal V.
AU  - van der Meulen, Nicholas P.
AU  - Talip, Zeynep
AU  - Ramaekers, Stijn
AU  - Van de Voorde, Michiel
AU  - Ponsard, Bernard
AU  - Casini, Angela
AU  - Günther, Thomas
TI  - Preclinical Evaluation of Gastrin-Releasing Peptide Receptor Antagonists Labeled with <sup>161</sup>Tb and <sup>177</sup>Lu: A Comparative Study
AID  - 10.2967/jnumed.123.266233
DP  - 2024 Mar 01
TA  - Journal of Nuclear Medicine
PG  - 481--484
VI  - 65
IP  - 3
4099  - http://jnm.snmjournals.org/content/65/3/481.short
4100  - http://jnm.snmjournals.org/content/65/3/481.full
SO  - J Nucl Med2024 Mar 01; 65
AB  - To elucidate potential benefits of the Auger-electron–emitting radionuclide 161Tb, we compared the preclinical performance of the gastrin-releasing peptide receptor antagonists RM2 (DOTA-Pip5-d-Phe6-Gln7-Trp8-Ala9-Val10-Gly11-His12-Sta13-Leu14-NH2) and AMTG (α-Me-Trp8-RM2), each labeled with both 177Lu and 161Tb. Methods: 161Tb/177Lu 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]: [161Tb]Tb-RM2, 2.46 ± 0.16; [161Tb]Tb-AMTG, 2.16 ± 0.09; [177Lu]Lu-RM2, 3.45 ± 0.18; [177Lu]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, [161Tb]Tb-/[177Lu]Lu-AMTG might reveal a higher therapeutic efficacy than [161Tb]Tb-/[177Lu]Lu-RM2, particularly [161Tb]Tb-AMTG because of additional Auger-electron emissions at the cell membrane level.