PSMA Receptor-Based PET-CT: The Basics and Current Status in Clinical and Research Applications

Prostate-specific membrane antigen (PSMA) is a 100 kD, 750 amino acid (AA) long type II transmembrane glycoprotein that has a short N-terminal intracellular domain with 19 AA, 24 AA transmembrane proteins and a large C-terminal extracellular domain with 707 AA. PSMA has been mapped to chromosome 11p 11-12 in the region of the folate hydrolase gene (FOLH1) and has no known natural ligand. The protein possesses enzymatic activity-glutamate carboxypeptidase II (GCP-II)-and is thought to have role in folate uptake (FOLH1 gene). 'PSMA' expression, although significantly up-regulated in prostate carcinoma (more in high-risk and aggressive variants), is not exclusive for it and is noted in various other benign and malignant conditions, especially in the neovasculature. Currently, PSMA PET-CT is approved for high-risk and biochemically recurrent prostate carcinoma (PCa), and in patient selection for PSMA based theranostics. This review aims to highlight the clinical evolution of the PSMA molecule and PSMA PET-CT as a diagnostic modality, various indications of PSMA PET-CT, the appropriateness criteria for its use, pitfalls and artefacts, and other uses of PSMA PET apart from prostate carcinoma.