Preclinical evaluation of gastrin-releasing peptide receptor antagonists labeled with &lt;sup&gt;161&lt;/sup&gt;Tb and &lt;sup&gt;177&lt;/sup&gt;Lu: a comparative study

Holzleitner, Nadine; Cwojdzinski, Tatjana; Beck, Roswitha; Urtz-Urban, Nicole; Hillhouse, Colin C.; Grundler, Pascal V.; van der Meulen, Nicholas P.; Talip, Zeynep; Ramaekers, Stijn; Van de Voorde, Michiel; Ponsard, Bernard; Casini, Angela; Günther, Thomas

doi:10.2967/jnumed.123.266233

Preclinical evaluation of gastrin-releasing peptide receptor antagonists labeled with ¹⁶¹Tb and ¹⁷⁷Lu: a comparative study

Holzleitner N, Cwojdzinski T, Beck R, Urtz-Urban N, Hillhouse CC, Grundler PV, van der Meulen NP, Talip Z, Ramaekers S, Van de Voorde M, Ponsard B, Casini A & Günther T

Citation

Holzleitner, N., Cwojdzinski, T., Beck, R., Urtz-Urban, N., Hillhouse, C. C., Grundler, P. V., … Günther, T. (2024). Preclinical evaluation of gastrin-releasing peptide receptor antagonists labeled with ¹⁶¹Tb and ¹⁷⁷Lu: a comparative study. Journal of Nuclear Medicine, 65(3), 481-484. https://doi.org/10.2967/jnumed.123.266233

Persistent URL https://www.dora.lib4ri.ch/psi/islandora/object/psi:61000

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-DPhe⁶-Gln⁷-Trp⁸-Ala⁹-Val¹⁰-Gly¹¹-His¹²-Sta¹³-Leu¹⁴-NH₂) and AMTG (a-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 6 0.16; [¹⁶¹Tb]Tb-AMTG, 2.16 6 0.09; [¹⁷⁷Lu]Lu-RM2, 3.45 6 0.18; [¹⁷⁷Lu]Lu-AMTG, 3.04 6 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.