Discovery of Glutamate Carboxypeptidase III Ligands to Compete the Uptake of [177Lu]Lu-PSMA-617 in Healthy Organs

• Published in: Journal of medicinal chemistry Vol. 67; no. 10; pp. 8247 - 8260
• Main Authors: Müller, Marco, Lucaroni, Laura, Favalli, Nicholas, Bassi, Gabriele, Neri, Dario, Cazzamalli, Samuele, Oehler, Sebastian
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 23.05.2024; Amer Chemical Soc
• Subjects: Antigens, Surface; Autoradiography; Chemistry, Medicinal; Dipeptides - chemistry; Dipeptides - metabolism; Glutamate Carboxypeptidase II; Heterocyclic Compounds, 1-Ring - chemistry; Heterocyclic Compounds, 1-Ring - metabolism; Humans; Life Sciences & Biomedicine; Ligands; Lutetium - chemistry; Lutetium - metabolism; Pharmacology & Pharmacy; Prostate-Specific Antigen; Radioisotopes - chemistry; Radioisotopes - metabolism; Radiopharmaceuticals - chemistry; Radiopharmaceuticals - metabolism; Radiopharmaceuticals - pharmacokinetics; Salivary Glands - metabolism; Science & Technology; Structure-Activity Relationship; Tissue Distribution; RADIOLIGAND THERAPY; BOTULINUM TOXIN; MEMBRANE ANTIGEN

Prostate-specific membrane antigen (PSMA)-targeted radio ligand therapeutics (RLTs), such as [177Lu]­Lu-PSMA-617 (Pluvicto), have been shown to accumulate in salivary glands and kidneys, potentially leading to undesired side effects. As unwanted accumulation in normal organs may derive from the cros...