Imaging Prostate Cancer: Clinical Utility of Prostate-Specific Membrane Antigen

Abstract

Purpose: Our goal was to review the pathway and pertinent materials leading to approval of prostate-specific membrane antigen (PSMA) scanning by the U.S. Food and Drug Administration (FDA). Materials and Methods: Beginning with the pivotal trials and working backward, we summarize the evolution of PSMA scanning, beginning with the discovery of the molecule, the mechanism of action to identify prostate cancer, the route to the present-day test and some of the major publications leading to each step of the sequence. From the thousands of PSMA articles listed on PubMedÒ, the present review is focused on the 4 large U.S. trials incorporating university studies of the gallium-68 compound and commercial studies of the fluorine-18 compound. The review further focuses on the role of PSMA scanning for both initial staging of prostate cancer and diagnosis of recurrent prostate cancer. Results: PSMA is a transmembrane-bound glycoprotein which is overexpressed by 100e1,000-fold in prostate cancer cells. Preclinical PSMA studies at Cornell and Johns Hopkins in the 1990s were followed by early human studies in Germany in the early 2010s, then pivotal clinical trials at

Focal therapy of prostate cancer: Assessment with prostate-specific membrane antigen (PSMA) imaging

“…Six months later a commercially-available agent ( 18 F-PSMA-1007) was also cleared. 2 Approved indications for both PSMA forms are (1) staging of PCa and (2) detection of recurrent PCa after definitive primary treatment. The present report confirms the work of Emmett 3 and others, showing that PSMA uptake can reveal localized cancer within the prostate and serve as a biopsy target when MRI fails to disclose the lesion.…”

“…1 In this report, a man with a falsely negative MRI underwent imaging with a different modality, radioisotope scanning with prostate-specific membrane antigen (PSMA, 68 Ga-PSMA-11 PET/CT). 2 PSMA-imaging was used to guide biopsy-detection of the PCa; to guide treatment of the cancer focally with high-intensity ultrasound (HIFU); and to show treatment success in follow-up, suggesting a possible new application for PSMA imaging.…”

Lu-177-Labeled Hetero-Bivalent Agents Targeting PSMA and Bone Metastases for Radionuclide Therapy

“…%). 1 (10). Compound 10 was prepared from 9 (320 mg, 0.415 mmol), DIPEA (155 mg, 1.2 mmol), HOBt (100 mg, 0.6 mmol), EDC (114 mg, 0.6 mmol), and Glu-NH-CO-NH-Lys-Phe-NH 2 (261 mg, 0.415 mmol) following the same procedure described for compound 5.…”

“…Prostate-specific membrane antigen (PSMA), also known as glutamate carboxypeptidase II (GCPII), is a cell-surface enzyme overexpressed on prostate cancer cells, making it an excellent target for PSMA-targeted diagnostic and therapeutic agents. Indeed, its potential for diagnosis and radionuclide treatment of prostate cancer has been demonstrated and well-reviewed. − Recently, FDA has approved [ 68 Ga]­Ga-PSMA-11 (Ga68 gozetotide), − [ 18 F]­DCFPyL (PYLARIFY, piflufolastat F18) − and [ 18 F]-rhPSMA-7.3 (POSLUMA, flotufolastat F 18) , for diagnostic imaging. PSMA PET scans are now being considered as a routine clinical procedure by urologists and oncologists for the diagnosis of prostate cancer.…”