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

[(177)Lu]Lu-AMTG 的首次人体血清稳定性研究:迈向改进 GRPR 靶向放射性药物治疗的一步

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Abstract

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

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