PSMA-Targeted Radiopharmaceuticals for Imaging and Therapy

As described in more detail in other contributions in this issue of Seminars in Nuclear Medicine, prostate-specific membrane antigen (PSMA) has become one of the most promising molecular targets in nuclear medicine. Due to its overexpression on prostate cancer cells in proportion to the stage and grade of tumour progression, especially in androgen-independent, advanced and metastatic disease, various tracers for the detection and treatment of prostate cancer by means of radioligand imaging, radioligand therapy or radioguided surgery have been developed and transferred to clinical applications. Even though monoclonal antibodies were investigated and introduced as first PSMA-targeted probes, the inherent advantage of fast tumour uptake and rapid excretion of small molecules has shifted the research focus during the last decade to low molecular weight inhibitors with high affinity to PSMA, such as [18F]FDCFPyL, [18F]PSMA-1007, [68Ga]PSMA-HBED, [177Lu]PSMA-617, [177Lu]PSMA-I&T, [99mTc]MIP-1404 or [99mTc]PSMA I&S, to mention only a few. Due to the plethora of such PSMA probes described during the last years, this review aims to give an overview over the specific characteristics of those radiopharmaceuticals that have already found widespread clinical application. In addition, recently introduced concepts such as PSMA-tracers with increased plasma protein binding, are discussed.