479: Prostate-Specific Membrane Antigen (PSMA) Expression as a Predictor of Prostate Cancer Progression

Abstract Introduction Fibroblast activation protein (FAP) has been recently presented as new imaging target for malignant diseases and offers high contrast to surrounding normal tissue. FAP tracer uptake has been reported in various tumor entities. The aim of this study was to compare FAP and Prostate-specific membrane antigen (PSMA) expression in primary prostate cancer employing histological analyses and PET imaging in two small patient collectives. Methods Two independent small patient collectives were included in this study. For cohort A, data of 5 prostate cancer patients and 3 patients with benign prostate hyperplasia were included. Patients with prostate cancer were initially referred for PSMA PET staging. Radical prostatectomy was performed in all patients and prostate specimen of patients and biopsies of healthy controls were available for further evaluation. Histological workup included HE and immunohistochemistry using PSMA Ab, FAP Ab. Cohort B consists of 6 Patients with diagnosed mCRPC and available PSMA as well as FAP PET. Results Patients with proven prostate cancer infiltration exhibited strong positivity for PSMA in both primary tumors and lymph node metastases while stainings for FAP were found positive in some cases, but not all (2/5). Controls with BPH presented moderate PSMA staining and in one case also with a positive FAP staining (1/3). PET imaging with FAP seemed to result in more precise results in case of low PSMA expression than PSMA-PET. Conclusions While PSMA staining intensity is a valid indicator of prostate cancer in both primary tumor and lymph node metastases, the expression of FAP seems to be heterogeneous but not necessarily linked to cancer-associated fibroblasts. It is also present in inflammation-associated myofibroblasts. Therefore, its ultimate role in prostate cancer diagnosis remains a subject of discussion.

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Heterogeneity of prostate-specific membrane antigen (PSMA) expression in classic and apoptotic circulating tumor cells (CTC) in metastatic castration-resistant prostate cancer (mCRPC).

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.198 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 198-198 ◽

Cited By ~ 1

Author(s):

Karen A. Autio ◽

Aseem Anand ◽

Rachel Krupa ◽

Jessica Louw ◽

Zaina Arslan ◽

...

Keyword(s):

Prostate Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Specific Antigen ◽

Cytotoxic Agents ◽

Prostate Specific Membrane Antigen ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Specific Membrane ◽

Psma Expression

198 Background: Prostate-specific membrane antigen (PSMA) is a folate hydrolase expressed on the surface of PC cells that has been used as a target to detect disease and selectively deliver cytotoxic agents and radionuclides. The ability to detect PSMA levels on circulating tumor cells (CTCs) may identify patients likely to benefit from such targeted therapy. Technology developed by Epic Sciences utilizes high definition imaging of plated nucleated cells. Methods: Blood samples were obtained from patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). Cells were stained for CK, CD45, PSMA and categorized as classic CTC (CK+, CD45-, intact/morphologically distinct nuclei) or apoptotic CTC (CK+, CD45-, morphology suggesting apoptosis). Clinical data including treatment, metastatic sites, Veridex CellSearch CTC enumeration, prostate-specific antigen, and alkaline phosphatase was collected. Results: Fourteen pts with mCRPC, including eight with serial samples were analyzed (33 samples in total). At the first draw (t1), classic CTC were detected in 13 pts (93%), (median two cells/ml, range 0 to 40 cells/ml) and apoptotic CTC in 14 pts (100%) (median four cells/ml, range 1 to 18 cells/ml), including six pts (42%) with no CTC by Veridex CellSearch. PSMA expression was detected in five pts (36%) with classic CTC of which a median of 32% of cells (range 5 to 100%) expressed the antigen. Similar intra-patient heterogeneity was seen for the 10 pts (71.4%) with PSMA+ apoptotic CTCs (median 33.5%, range 11 to 75% cells). During treatment, often with more complete androgen suppression, PSMA was detected in 3 of the 8 (38%) pts with no PSMA+ classic CTCs at t1. The presence of PSMA expression in apoptotic CTCs did not appear to change while on therapy. Conclusions: A larger percentage of PSMA expression was seen in mCRPC pts in apoptotic CTC (10 out of 14) than classic CTC (5 out of 14) at t1, with intra-patient cell heterogeneity of PSMA expression in both CTC populations. Serial measures suggest dynamic changes in PSMA expression over time. The threshold of detectable cells and proportion and degree of PSMA expression that associates with drug sensitivity is unknown. Larger samples of pts at discrete time points on therapy are underway to further elucidate the potential clinical relevance.

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Alterations in androgen deprivation enhanced prostate-specific membrane antigen (PSMA) expression in prostate cancer cells as a target for diagnostics and therapy

EJNMMI Research ◽

10.1186/s13550-015-0145-8 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 56

Author(s):

B. Meller ◽

F. Bremmer ◽

C. O. Sahlmann ◽

S. Hijazi ◽

C. Bouter ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Androgen Deprivation ◽

Prostate Specific Membrane Antigen ◽

Prostate Cancer Cells ◽

Specific Membrane ◽

Psma Expression ◽

Diagnostics And Therapy

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Poor Outcomes for Patients with Metastatic Castration-resistant Prostate Cancer with Low Prostate-specific Membrane Antigen (PSMA) Expression Deemed Ineligible for 177Lu-labelled PSMA Radioligand Therapy

European Urology Oncology ◽

10.1016/j.euo.2018.11.007 ◽

2019 ◽

Vol 2 (6) ◽

pp. 670-676 ◽

Cited By ~ 19

Author(s):

Sue Ping Thang ◽

John Violet ◽

Shahneen Sandhu ◽

Amir Iravani ◽

Tim Akhurst ◽

...

Keyword(s):

Prostate Cancer ◽

Prostate Specific Membrane Antigen ◽

Castration Resistant Prostate Cancer ◽

Radioligand Therapy ◽

Castration Resistant ◽

Poor Outcomes ◽

Specific Membrane ◽

Psma Expression

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Prostate specific membrane antigen (PSMA) expression gives prostate cancer cells a growth advantage in a physiologically relevant folate environment in vitro

The Prostate ◽

10.1002/pros.20361 ◽

2006 ◽

Vol 66 (8) ◽

pp. 867-875 ◽

Cited By ~ 26

Author(s):

Veronica Yao ◽

Dean J. Bacich

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Prostate Specific Membrane Antigen ◽

Prostate Cancer Cells ◽

Specific Membrane ◽

Psma Expression

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Prostate-Specific Membrane Antigen Uptake and Survival in Metastatic Castration-Resistant Prostate Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.630589 ◽

2021 ◽

Vol 11 ◽

Author(s):

Panagiotis J. Vlachostergios ◽

Muhammad Junaid Niaz ◽

Michael Sun ◽

Seyed Ali Mosallaie ◽

Charlene Thomas ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Emission Computed Tomography ◽

Prostate Specific Membrane Antigen ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Pet Ct ◽

Specific Membrane ◽

Psma Expression ◽

Systemic Therapies

BackgroundProstate-specific membrane antigen (PSMA) imaging has been suggested as highly sensitive modality for detection of metastases in patients with biochemically recurrent or advanced prostate cancer (PCa). PSMA expression is associated with grade and stage and has a relationship with androgen receptor signaling. The aim of this study was to evaluate the prognostic utility of radiographic PSMA expression in men with metastatic castration-resistant prostate cancer (mCRPC).MethodsPatients with mCRPC and available baseline PSMA imaging were studied. Images by planar/single-photon emission computed tomography (SPECT) or positron emission tomography (PET)/CT were reviewed. Planar/SPECT images were scored semi-quantitatively and PET/CT scored quantitatively with comparison of tumor uptake to liver uptake on a scale of 0–4 in order to determine an imaging score (IS). The IS (high: 2–4 versus low: 0–1), subsequent receipt of life-prolonging systemic therapies (taxane chemotherapy, potent androgen receptor pathway inhibitors, sipuleucel-T, and radium-223), and the CALGB prognostic risk stratification of patients were analyzed according to overall survival (OS) in univariate and multivariate Cox’s proportional hazards models.ResultsHigh PSMA expression (IS 2–4) was found in 179 (75.21%) patients, and 59 (24.79%) patients had low PSMA uptake. The median OS of the entire cohort was 16.8 (95%CI: 14.9–19.3) months. Patients with a high IS had a significantly shorter OS of 15.8 (95%CI 13.0–18.1) months compared to those with low expression [22.7 (95%CI: 17.7–30.7) months, p = 0.002]. After accounting for use of life-prolonging therapies (p<0.001) and CALGB prognostic groups (p = 0.001), high PSMA IS emerged as an independent prognostic factor for OS [HR(95%CI): 1.7 (1.2–2.2); p = 0.003].ConclusionPresence of high radiographic PSMA expression on SPECT or PET/CT may portend a poor prognosis in patients with mCRPC treated with standard systemic therapies. This provides implications for therapeutic targeting of PSMA-avid disease as a means to improve outcomes.

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Magnetic polymeric nanobubbles with optimized core size for MRI/ultrasound bimodal molecular imaging of prostate cancer

Nanomedicine ◽

10.2217/nnm-2020-0188 ◽

2020 ◽

Vol 15 (30) ◽

pp. 2901-2916

Author(s):

Yunkai Zhu ◽

Ying Sun ◽

Weiyong Liu ◽

Wenbin Guan ◽

Huanhuan Liu ◽

...

Keyword(s):

Prostate Cancer ◽

Physical Property ◽

Prostate Specific Membrane Antigen ◽

Core Size ◽

Dual Modality ◽

Imaging Probes ◽

Dual Modality Imaging ◽

Histopathologic Findings ◽

Specific Membrane ◽

Psma Expression

Aim: To design MRI/ultrasound (US) dual modality imaging probes with optimized size for prostate cancer imaging by targeting prostate-specific membrane antigen (PSMA). Materials & methods: The PSMA-targeting polypeptide-nanobubbles (PP-NBs) with core size of 400 and 700 nm were fabricated and evaluated. Results: With excellent physical property and specificity, PP-NBs of both core size could image PSMA expression in prostate cancer xenografts. Particularly, 400 nm PP-NBs generated higher PSMA-specific MRI/US dual modality contrast enhancement than 700 nm PP-NBs in correlation with histopathologic findings. Conclusion: Benefit from the smaller core size, 400 nm PP-NBs had higher permeability and specificity than 700 nm PP-NBs, hence producing better PSMA-specific MRI/US dual modality imaging.

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