The Rise of PSMA Ligands for Diagnosis and Therapy of Prostate Cancer.
The prostate-specific membrane antigen (PSMA) has received increased consideration during the past few years as an excellent target for both imaging and therapy of prostate cancer. After many years of outstanding preclinical research, the first significant step forward in clinical use was achieved in 2008 with the first human experience with the small-molecule PSMA inhibitors123I-MIP-1972 and123I-MIP-1095. A clinical breakthrough followed in 2011 with68Ga-PSMA-11 for PET imaging and131I-MIP-1095 for endoradiotherapy of metastatic prostate cancer. Since then, PET/CT with68Ga-PSMA-11 has rapidly spread worldwide, and endoradiotherapy with PSMA ligands has been conducted at increasing numbers of centers.68Ga-PSMA-11 is currently the subject of multicenter studies in different countries. Since 2013,131I-related PSMA therapy has been replaced by177Lu-labeled ligands, such as PSMA-617, which is also the subject of multicenter studies. Alternative PSMA ligands for both imaging and therapy are available. Among them is99mTc-MIP-1404, which has recently entered a phase 3 clinical trial. This article focuses on the highlights of the development and clinical application of PSMA ligands.
Department of Nuclear Medicine, Heidelberg University Hospital, Heidelberg, Germany Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg, Germany a.afshar@gmx.de.
Ali
A
Afshar-Oromieh
Division of Radiopharmaceutical Sciences, Department of Radiology, Weill Cornell Medicine, New York, New York.
John W
JW
Babich
Department of Nuclear Medicine, Heidelberg University Hospital, Heidelberg, Germany.
Clemens
C
Kratochwil
Department of Nuclear Medicine, Heidelberg University Hospital, Heidelberg, Germany German Cancer Consortium (DKTK), Heidelberg, Germany; and.
Frederik L
FL
Giesel
Division of Radiopharmaceutical Chemistry, German Cancer Research Center, Heidelberg, Germany.
Michael
M
Eisenhut
German Cancer Consortium (DKTK), Heidelberg, Germany; and Division of Radiopharmaceutical Chemistry, German Cancer Research Center, Heidelberg, Germany.
Klaus
K
Kopka
Department of Nuclear Medicine, Heidelberg University Hospital, Heidelberg, Germany Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg, Germany German Cancer Consortium (DKTK), Heidelberg, Germany; and.
Uwe
U
Haberkorn
D000954:Antigens, Surface / Q000378:metabolism*; D004151:Dipeptides / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D019317:Evidence-Based Medicine; D043425:Glutamate Carboxypeptidase II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006573:Heterocyclic Compounds, 1-Ring / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006801:Humans; D007089:Image Enhancement; D008297:Male; D025202:Molecular Diagnostic Techniques; D058990:Molecular Targeted Therapy; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use; D049268:Positron-Emission Tomography; D017430:Prostate-Specific Antigen; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000532:radiotherapy*; D019275:Radiopharmaceuticals
D000954:Antigens, Surface; D004151:Dipeptides; D006573:Heterocyclic Compounds, 1-Ring; D015609:Organotechnetium Compounds; C000602389:PSMA-617; D019275:Radiopharmaceuticals; C000595576:technetium 99m 1-(1-(2-(bis(carboxymethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)-2-((1-(2-(bis(carboxymethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)-9,14-dioxo-2,8,13,15-tetraazaoctadecane-7,12,16,18-tetracarboxylic acid); C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D017430:Prostate-Specific Antigen
PET/CT; PSMA; endoradiotherapy; prostate cancer; prostate-specific membrane antigen