PSMA targeting in prostate cancer


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Matthias Eiber1
1Technical University Munich - Dept. of Nuclear Medicine

Abstract

Background

Prostate cancer (PC) is one of the most common malignancies in the world. Imaging is increasingly be used over the last two decades to improve staging prior initial therapy and help localization tumor deposits in recurrent disease. However, sensitivity of morphology based imaging in certain clinical scenarios (detection of lymph node metastases and early biochemical recurrence) is limited. In addition, despite the development of multiple new treatment options the overall survival of patients with metastastic castration resistant prostate cancer is still liminted. In the last few year the use of agents targeting the prostate-specific membrane antigen (PSMA) has become increasing attention. PSMA is a type II transmembrane protein, and PSMA expression and localization in the normal human prostate is associated with the cytoplasm and apical side of the epithelium surrounding prostatic ducts. PSMA is an ideal target in PC-imaging: 1. It shows significant (100-1000 fold) over-expression on nearly all prostatic cancer cells. 5-10% of primary PC or PC lesions have shown to be PSMA-PET negative 2. Its expression is further increased in advanced stages and in CRPC 3. After binding to the active extracellular center PSMA-ligands are internalized. Subsequent endosomal recycling increases the deposition of binding substrates leading to enhanced tumor uptake and retention and subsequent high image quality for diagnostic procedures and a high local dose for therapeutic applications. Contents of the talk will include: 1.The molecular basis of prostate cancer imaging targeting the prostate-specific-membran antigen (PSMA), review of the various PSMA-tracers 2.The diagnostic performance and potential role of PSMA PET for high-risk primary and biochemical recurrent prostate cancer 3.Role and current evidence for PSMA-targeted endoradiotherapy.