Glutamate carboxypeptidase 2 (PSMA) (PSMA)

Glutamate carboxypeptidase 2 (PSMA) is a type II transmembrane glycoprotein that functions as a zinc-dependent metalloenzyme [UniProt: Q04609]. In the nervous system, it hydrolyzes the neurotransmitter N-acetylaspartylglutamate (NAAG), while in the intestine, it acts as a folate hydrolase to enable folate absorption [PubMed: 34534489]. PSMA is highly overexpressed in prostate cancer cells, especially in metastatic and castration-resistant cases, making it a premier target for diagnostic imaging and therapy [PubMed: 34534489]. While its expression is high in malignant prostate tissue, it is also found in the neovasculature of other solid tumors and limited normal tissues like the salivary glands and kidneys [StatPearls: NBK574501]. Modern therapeutic approaches use small-molecule ligands or antibodies conjugated to radionuclides, such as Lutetium-177, which bind to the extracellular domain and are internalized [FDA: Pluvicto]. This internalization process allows for the concentrated delivery of radiation or cytotoxic drugs directly into the tumor cells [PubMed: 34534489]. As a result, PSMA-targeted agents have revolutionized the theranostic approach to prostate cancer management [PubMed: 34534489].

Other names

Prostate-specific membrane antigenFOLH1Folate hydrolase 1N-acetyl-alpha-linked acidic dipeptidase INAALADase IGCPII

Radioligand therapy and diagnostic imaging via high-affinity binding to the extracellular domain of PSMA, followed by receptor-mediated internalization (endocytosis) which sequesters the therapeutic or diagnostic agent within the cell [PubMed: 34534489].