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

• Published in: Journal of Nuclear Medicine Vol. 66; no. 6; pp. 896 - 899
• Main Authors: Felber, Veronika, Holzleitner, Nadine, Joksch, Markus, Suhrbier, Tim, von Amsberg, Gunhild, Schwarzenböck, Sarah, Kurth, Jens, Heuschkel, Martin, Günther, Thomas, Krause, Bernd J.
• Format: Journal Article
• Language: English
• Published: United States 01.06.2025
• Subjects: Drug Stability; Humans; Lutetium - chemistry; Lutetium - therapeutic use; Male; Molecular Targeted Therapy; Positron Emission Tomography Computed Tomography; Radioisotopes - therapeutic use; Radiopharmaceuticals - blood; Radiopharmaceuticals - chemistry; Radiopharmaceuticals - pharmacokinetics; Radiopharmaceuticals - therapeutic use; Receptors, Bombesin - metabolism; AMTG; first-in-human; GRPR; in vivo serum stability; 177Lu
• ISSN: 0161-5505; 2159-662X; 1535-5667
• DOI: 10.2967/jnumed.124.269132

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.