title: Radiolabeled enzyme inhibitors and binding agents targeting PSMA: Effective theranostic tools for imaging and therapy of prostate cancer.
abstract: Because of the broad incidence, morbidity and mortality associated with prostate-derived cancer, the development of more effective new technologies continues to be an important goal for the accurate detection and treatment of localized prostate cancer, lymphatic involvement and metastases. Prostate-specific membrane antigen (PSMA; Glycoprotein II) is expressed in high levels on prostate-derived cells and is an important target for visualization and treatment of prostate cancer. Radiolabeled peptide targeting technologies have rapidly evolved over the last decade and have focused on the successful development of radiolabeled small molecules that act as inhibitors to the binding of the N-acetyl-l-aspartyl-l-glutamate (NAAG) substrate to the PSMA molecule. A number of radiolabeled PSMA inhibitors have been described in the literature and labeled with SPECT, PET and therapeutic radionuclides. Clinical studies with these agents have demonstrated the improved potential of PSMA-targeted PET imaging agents to detect metastatic prostate cancer in comparison with conventional imaging technologies. Although many of these agents have been evaluated in humans, by far the most extensive clinical literature has described use of the68Ga and177Lu agents. This review describes the design and development of these agents, with a focus on the broad clinical introduction of PSMA targeting motifs labeled with68Ga for PET-CT imaging and177Lu for therapy. In particular, because of availability from the long-lived68Ge (T1/2=270days)/68Ga (T1/2=68min) generator system and increasing availability of PET-CT, the68Ga-labeled PSMA targeted agent is receiving widespread interest and is one of the fastest growing radiopharmaceuticals for PET-CT imaging.
authors: Molecular Group of Companies, Puthuvype, Ernakulam, Kerala, 682508, India. Electronic address: pillai.m.r.a@gmail.com.
authors: Maroor Raghavan Ambikalmajan
authors: MRA
authors: Pillai
authors: KIMS DDNMRC PET Scans, KIMS Hospital, Trivandrum, Kerala, India, 691601.
authors: Raviteja
authors: R
authors: Nanabala
authors: Molecular Group of Companies, Puthuvype, Ernakulam, Kerala, 682508, India.
authors: Ajith
authors: A
authors: Joy
authors: KIMS DDNMRC PET Scans, KIMS Hospital, Trivandrum, Kerala, India, 691601.
authors: Arun
authors: A
authors: Sasikumar
authors: Emeritus, Medical Radioisotope Program, Oak Ridge National Laboratory, Oak Ridge, TN, USA, 37830.
authors: Furn F
authors: FF
authors: Russ Knapp
mesh_terms: D000954:Antigens, Surface / Q000378:metabolism*; D003952:Diagnostic Imaging / Q000379:methods*; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D043425:Glutamate Carboxypeptidase II / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
chemical_list: D000954:Antigens, Surface; D004791:Enzyme Inhibitors; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II
keywords: Enzyme inhibitors; Gallium-68; Lutetium-177; Prostate cancer; Prostate-specific membrane antigen; Targeted radionuclide therapy