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

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