First-in-Human Serum Stability Studies of [<sup>177</sup>Lu]Lu-AMTG: A Step Toward Improved GRPR-Targeted Radiopharmaceutical Therapy.

Felber, Veronika; Holzleitner, Nadine; Joksch, Markus; Suhrbier, Tim; von Amsberg, Gunhild; Schwarzenböck, Sarah; Kurth, Jens; Heuschkel, Martin et al. · J Nucl Med · 2025

Where this comes from

Abstract

The use of PET/CT with gastrin-releasing peptide receptor (GRPR) ligand [<sup>68</sup>Ga]Ga-AMTG has recently been shown to diagnose metastatic disease not detected by <sup>18</sup>F-PSMA PET/CT in patients with metastatic castration-resistant prostate cancer. This study aimed to analyze the serum stability of [<sup>177</sup>Lu]Lu-AMTG in human subjects due to the compound's high stability observed preclinically and to elucidate its therapeutic potential. <b>Methods:</b> Blood samples were collected at various time points after intravenous injection of 7.6 ± 0.1 GBq of [<sup>177</sup>Lu]Lu-AMTG and centrifuged. Serum samples were analyzed via reversed-phase high-performance liquid chromatography. <b>Results:</b> At 1 h after injection, the mean ± SD in vivo serum stability of [<sup>177</sup>Lu]Lu-AMTG was distinctly higher (62% ± 6%) than that of [<sup>68</sup>Ga]Ga-RM2 (19% ± 2%). <b>Conclusion:</b> Based on the high in vivo serum stability of [<sup>177</sup>Lu]Lu-AMTG in humans and favorable biodistribution, radiolabeled AMTG derivatives have the potential to improve radiopharmaceutical therapy for GRPR-expressing malignancies.

Medical subject headings