Prostate-specific membrane antigen expression is greatest in prostate adenocarcinoma and lymph node metastases

Sweat, Susan D.; Pacelli, Anna; Murphy, Gerald P.; Bostwick, David G.

doi:10.1016/s0090-4295(98)00278-7

Cited by 513 publications

(303 citation statements)

References 16 publications

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“…[3][4][5] Recent studies have demonstrated variable levels of FH(PSA)1 expression in numerous other tissue types, including cardiac tissue, pancreatic islet cells, lung adenocarcinoma, gastric cancer and colorectal cancer. 6 Some studies have demonstrated FH(PSA)1 expression in the normal urothelium; however, conflicting results make the true expression pattern unclear.…”

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confidence: 99%

Folate hydrolase (prostate-specific antigen) 1 expression in bladder cancer subtypes and associated tumor neovasculature

et al. 2011

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Folate hydrolase (prostate-specific antigen) 1 expression in bladder cancer subtypes and associated tumor neovasculature

et al. 2011

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“…However, especially in patients with PSA values below 3 ng/mL, the detection rate is only 40%-60% (3,4,7). Recently, a new molecular probe targeting, for example, the gastrinreleasing peptide receptor or the prostate-specific membrane antigen (PSMA), has been developed (10)(11)(12). PSMA is a membrane-bound enzyme with significantly elevated expression in PC cells in comparison to benign prostatic tissue (13).…”

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confidence: 99%

Evaluation of Hybrid ⁶⁸Ga-PSMA Ligand PET/CT in 248 Patients with Biochemical Recurrence After Radical Prostatectomy

et al. 2015

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The expression of prostate-specific membrane antigen (PSMA) is increased in prostate cancer. Recently, 68 Ga-PSMA (Glu-NH-CO-NH-Lys-(Ahx)-[ 68 Ga(HBED-CC)]) was developed as a PSMA ligand. The aim of this study was to investigate the detection rate of 68 Ga-PSMA PET/CT in patients with biochemical recurrence after radical prostatectomy. Methods: Two hundred forty-eight of 393 patients were evaluable for a retrospective analysis. Median prostate-specific antigen (PSA) level was 1.99 ng/mL (range, 0.2-59.4 ng/mL). All patients underwent contrast-enhanced PET/CT after injection of 155 ± 27 MBq of 68 Ga-PSMA ligand. The detection rates were correlated with PSA level and PSA kinetics. The influence of antihormonal treatment, primary Gleason score, and contribution of PET and morphologic imaging to the final diagnosis were assessed. Results: Two hundred twenty-two (89.5%) patients showed pathologic findings in 68 Ga-PSMA ligand PET/CT. The detection rates were 96.8%, 93.0%, 72.7%, and 57.9% for PSA levels of $2, 1 to ,2, 0.5 to ,1, and 0.2 to ,0.5 ng/mL, respectively. Whereas detection rates increased with a higher PSA velocity (81.8%, 82.4%, 92.1%, and 100% in ,1, 1 to ,2, 2 to ,5, and $5 ng/mL/y, respectively), no significant association could be found for PSA doubling time (82.7%, 96.2%, and 90.7% in .6, 4-6, and ,4 mo, respectively). 68 Ga-PSMA ligand PET (as compared with CT) exclusively provided pathologic findings in 81 (32.7%) patients. In 61 (24.6%) patients, it exclusively identified additional involved regions. In higher Gleason score (#7 vs. $8), detection efficacy was significantly increased (P 5 0.0190). No significant difference in detection efficacy was present regarding antiandrogen therapy (P 5 0.0783). Conclusion: Hybrid 68 Ga-PSMA ligand PET/CT shows substantially higher detection rates than reported for other imaging modalities. Most importantly, it reveals a high number of positive findings in the clinically important range of low PSA values (,0.5 ng/mL), which in many cases can substantially influence the further clinical management.

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“…1,2 PSMA is an attractive target for immunotherapy because it is highly expressed in normal and neoplastic prostatic tissue and the neovasculature of solid tumors, with limited expression in normal tissue. [3][4][5][6][7] PSMA-specific monoclonal antibodies (MAb) have been used for in vivo diagnostic and therapeutic applications without adverse events. [8][9][10][11] Biochemical and objective measurable disease responses were reported in some patients treated with radionuclide conjugates of a humanized MAb, J591, that binds to the extracellular domain of PSMA.…”

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Induction of autoantibodies to syngeneic prostate‐specific membrane antigen by xenogeneic vaccination

Gregor

Wolchok

Turaga

et al. 2005

Intl Journal of Cancer

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Prostate-specific membrane antigen (PSMA) is a prototypical differentiation antigen expressed on normal and neoplastic prostate epithelial cells, and on the neovasculature of many solid tumors. Monoclonal antibodies specific for PSMA are in development as therapeutic agents. Methodologies to actively immunize against PSMA may be limited by immunologic ignorance and/or tolerance that restrict the response to self-antigens. Our studies have previously shown that xenogeneic immunization with DNA vaccines encoding melanosomal differentiation antigens induces immunity in a mouse melanoma model. Here we apply this approach to PSMA to establish proof of principle in a mouse model. Immunization with xenogeneic human PSMA protein or DNA induced antibodies to both human and mouse PSMA in mice. Monoclonal antibodies specific for mouse PSMA were generated to analyze antibody isotypes and specificity for native and denatured PSMA at the clonal level. Most antibodies recognized denatured PSMA, but C57BL/6 mice immunized with xenogeneic PSMA DNA followed by a final boost with xenogeneic PSMA protein yielded autoantibodies that reacted with native folded mouse PSMA. Monoclonal antibodies were used to confirm the expression of PSMA protein in normal mouse kidney. These results establish the basis for clinical trials to test PSMA DNA vaccines in patients with solid tumors that either express PSMA directly or that depend on normal endothelial cells expressing PSMA for their continued growth. ' 2005 Wiley-Liss, Inc.

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Prostate-specific membrane antigen expression is greatest in prostate adenocarcinoma and lymph node metastases

Cited by 513 publications

References 16 publications

Folate hydrolase (prostate-specific antigen) 1 expression in bladder cancer subtypes and associated tumor neovasculature

Folate hydrolase (prostate-specific antigen) 1 expression in bladder cancer subtypes and associated tumor neovasculature

Evaluation of Hybrid ⁶⁸Ga-PSMA Ligand PET/CT in 248 Patients with Biochemical Recurrence After Radical Prostatectomy

Induction of autoantibodies to syngeneic prostate‐specific membrane antigen by xenogeneic vaccination

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Prostate-specific membrane antigen expression is greatest in prostate adenocarcinoma and lymph node metastases

Cited by 513 publications

References 16 publications

Folate hydrolase (prostate-specific antigen) 1 expression in bladder cancer subtypes and associated tumor neovasculature

Folate hydrolase (prostate-specific antigen) 1 expression in bladder cancer subtypes and associated tumor neovasculature

Evaluation of Hybrid 68Ga-PSMA Ligand PET/CT in 248 Patients with Biochemical Recurrence After Radical Prostatectomy

Induction of autoantibodies to syngeneic prostate‐specific membrane antigen by xenogeneic vaccination

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Evaluation of Hybrid ⁶⁸Ga-PSMA Ligand PET/CT in 248 Patients with Biochemical Recurrence After Radical Prostatectomy