Prostate-specific membrane antigen (PSMA), also known as glutamate carboxypeptidase II, is a type II transmembrane glycoprotein that has become an increasingly prominent imaging biomarker 1. PSMA has emerged as a useful target in PET imaging of prostate cancer, especially in the evaluation of small volume lymph node and bone metastases using tracers like Ga-68 PSMA (the first radiotracer to be approved by the FDA in December 2020) and F-18 PSMA 2,11. The theranostic agent Lutetium-177 vipivotide tetraxetan (trade name Pluvicto) used to treat metastatic castration-resistant prostate cancer obtained FDA approval in 2022 12.
PSMA's structure consists of 750 amino acids (100-120 kDa), with a 19-amino acid intracellular segment, a 24-amino acid intramembrane component and a 707-amino acid extracellular domain 1. It is encoded by the FOLH1 gene located on the short arm of chromosome 11 7.
Advantages
significantly overexpressed in prostate cancer tissue 2
expression is positively correlated with tumor grade, pathological stage and degree of disease recurrence 2
PSMA is internalised upon binding, resulting in enhanced tumor uptake and retention 3
ideal target for small-molecule radiopharmaceuticals 3 for both diagnostic imaging through PET and therapy
1.Israeli R, Powell C, Fair W, Heston W. Molecular Cloning of a Complementary DNA Encoding a Prostate-Specific Membrane Antigen. Cancer Res. 1993;53(2):227-30. - Pubmed
2. Hofman M & Iravani A. Gallium-68 Prostate-Specific Membrane Antigen PET Imaging. PET Clinics. 2017;12(2):219-34. doi:10.1016/j.cpet.2016.12.004 - Pubmed
3. Eder M, Eisenhut M, Babich J, Haberkorn U. PSMA as a Target for Radiolabelled Small Molecules. Eur J Nucl Med Mol Imaging. 2013;40(6):819-23. doi:10.1007/s00259-013-2374-2 - Pubmed
4. Silver D, Pellicer I, Fair W, Heston W, Cordon-Cardo C. Prostate-Specific Membrane Antigen Expression in Normal and Malignant Human Tissues. Clin Cancer Res. 1997;3(1):81-5. - Pubmed
5. Chang S, Reuter V, Heston W, Bander N, Grauer L, Gaudin P. Five Different Anti-Prostate-Specific Membrane Antigen (PSMA) Antibodies Confirm PSMA Expression in Tumor-Associated Neovasculature. Cancer Res. 1999;59(13):3192-8. - Pubmed
6. Haffner M, Kronberger I, Ross J et al. Prostate-Specific Membrane Antigen Expression in the Neovasculature of Gastric and Colorectal Cancers. Hum Pathol. 2009;40(12):1754-61. doi:10.1016/j.humpath.2009.06.003 - Pubmed
7. Leek J, Lench N, Maraj B et al. Prostate-Specific Membrane Antigen: Evidence for the Existence of a Second Related Human Gene. Br J Cancer. 1995;72(3):583-8. doi:10.1038/bjc.1995.377 - Pubmed
8. Hofman M, Hicks R, Maurer T, Eiber M. Prostate-Specific Membrane Antigen PET: Clinical Utility in Prostate Cancer, Normal Patterns, Pearls, and Pitfalls. Radiographics. 2018;38(1):200-17. doi:10.1148/rg.2018170108 - Pubmed
9. Shetty D, Patel D, Le K, Bui C, Mansberg R. Pitfalls in Gallium-68 PSMA PET/CT Interpretation-A Pictorial Review. Tomography. 2018;4(4):182-93. doi:10.18383/j.tom.2018.00021 - Pubmed
10. Foley R, Redman S, Graham R, Loughborough W, Little D. Fluorine-18 Labelled Prostate-Specific Membrane Antigen (PSMA)-1007 Positron-Emission Tomography-Computed Tomography: Normal Patterns, Pearls, and Pitfalls. Clin Radiol. 2020;75(12):903-13. doi:10.1016/j.crad.2020.06.031 - Pubmed
11. Evangelista L, Maurer T, van der Poel H et al. [Ga]Ga-PSMA Versus [F]PSMA Positron Emission Tomography/Computed Tomography in the Staging of Primary and Recurrent Prostate Cancer. A Systematic Review of the Literature. Eur Urol Oncol. 2022;5(3):273-82. doi:10.1016/j.euo.2022.03.004 - Pubmed
12. FDA Approves Pluvicto for Metastatic Castration-Resistant Prostate Caner. US Food and Drug Administration. Published 3.23.22. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pluvicto-metastatic-castration-resistant-prostate-cancer
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