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

Abstract

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