scholarly journals Neuroendocrine differentiation of prostate cancer leads to PSMA suppression

2019 ◽  
Vol 26 (2) ◽  
pp. 131-146 ◽  
Author(s):  
Martin K Bakht ◽  
Iulian Derecichei ◽  
Yinan Li ◽  
Rosa-Maria Ferraiuolo ◽  
Mark Dunning ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Molecular Imaging ◽  
Case Reports ◽  
Somatostatin Receptor ◽  
Neuroendocrine Differentiation ◽  
Transcript Abundance ◽  
Marker Genes ◽  
Targeted Imaging ◽  
Significant Suppression ◽  
Protein Alterations

Prostate-specific membrane antigen (PSMA) is overexpressed in most prostate adenocarcinoma (AdPC) cells and acts as a target for molecular imaging. However, some case reports indicate that PSMA-targeted imaging could be ineffectual for delineation of neuroendocrine (NE) prostate cancer (NEPC) lesions due to the suppression of the PSMA gene (FOLH1). These same reports suggest that targeting somatostatin receptor type 2 (SSTR2) could be an alternative diagnostic target for NEPC patients. This study evaluates the correlation between expression of FOLH1, NEPC marker genes and SSTR2. We evaluated the transcript abundance for FOLH1 and SSTR2 genes as well as NE markers across 909 tumors. A significant suppression of FOLH1 in NEPC patient samples and AdPC samples with high expression of NE marker genes was observed. We also investigated protein alterations of PSMA and SSTR2 in an NE-induced cell line derived by hormone depletion and lineage plasticity by loss of p53. PSMA is suppressed following NE induction and cellular plasticity in p53-deficient NEPC model. The PSMA-suppressed cells have more colony formation ability and resistance to enzalutamide treatment. Conversely, SSTR2 was only elevated following hormone depletion. In 18 NEPC patient-derived xenograft (PDX) models we find a significant suppression of FOLH1 and amplification of SSTR2 expression. Due to the observed FOLH1-supressed signature of NEPC, this study cautions on the reliability of using PMSA as a target for molecular imaging of NEPC. The observed elevation of SSTR2 in NEPC supports the possible ability of SSTR2-targeted imaging for follow-up imaging of low PSMA patients and monitoring for NEPC development.

scholarly journals Recent Updates on Molecular Imaging Reporting and Data Systems (MI-RADS) for Theranostic Radiotracers—Navigating Pitfalls of SSTR- and PSMA-Targeted PET/CT

2019 ◽  
Vol 8 (7) ◽  
pp. 1060 ◽  
Author(s):  
Rudolf A. Werner ◽  
James T. Thackeray ◽  
Martin G. Pomper ◽  
Frank M. Bengel ◽  
Michael A. Gorin ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Somatostatin Receptor ◽  
False Negative ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Subsequent Treatment ◽  
Targeted Imaging ◽  
Data Systems ◽  
Pet Ct ◽  
Framework System

The theranostic concept represents a paradigmatic example of personalized treatment. It is based on the use of radiolabeled compounds which can be applied for both diagnostic molecular imaging and subsequent treatment, using different radionuclides for labelling. Clinically relevant examples include somatostatin receptor (SSTR)-targeted imaging and therapy for the treatment of neuroendocrine tumors (NET), as well as prostate-specific membrane antigen (PSMA)-targeted imaging and therapy for the treatment of prostate cancer (PC). As such, both classes of radiotracers can be used to triage patients for theranostic endoradiotherapy using positron emission tomography (PET). While interpreting PSMA- or SSTR-targeted PET/computed tomography scans, the reader has to navigate certain pitfalls, including (I.) varying normal biodistribution between different PSMA- and SSTR-targeting PET radiotracers, (II.) varying radiotracer uptake in numerous kinds of both benign and malignant lesions, and (III.) resulting false-positive and false-negative findings. Thus, two novel reporting and data system (RADS) classifications for PSMA- and SSTR-targeted PET imaging (PSMA- and SSTR-RADS) have been recently introduced under the umbrella term molecular imaging reporting and data systems (MI-RADS). Notably, PSMA- and SSTR-RADS are structured in a reciprocal fashion, i.e., if the reader is familiar with one system, the other system can readily be applied. Learning objectives of the present case-based review are as follows: (I.) the theranostic concept for the treatment of NET and PC will be briefly introduced, (II.) the most common pitfalls on PSMA- and SSTR-targeted PET/CT will be identified, (III.) the novel framework system for theranostic radiotracers (MI-RADS) will be explained, applied to complex clinical cases and recent studies in the field will be highlighted. Finally, current treatment strategies based on MI-RADS will be proposed, which will demonstrate how such a generalizable framework system truly paves the way for clinically meaningful molecular imaging-guided treatment of either PC or NET. Thus, beyond an introduction of MI-RADS, the present review aims to provide an update of recently published studies which have further validated the concept of structured reporting systems in the field of theranostics.

Prognostic role of somatostatin receptor subtypes in human prostate cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16120-e16120
Author(s):  
A. Gernone ◽  
V. Pagliarulo ◽  
S. Trabucco
Keyword(s):  
Prostate Cancer ◽  
Single Cells ◽  
Performance Status ◽  
Somatostatin Receptor ◽  
Somatostatin Analogs ◽  
Neuroendocrine Differentiation ◽  
Patient Characteristics ◽  
Receptor Subtypes ◽  
Ecog Performance Status ◽  
Somatostatin Receptor Subtypes

e16120 Background: Neuroendocrine differentiation (NED) in prostate carcinoma (PC) is frequently detected by immunohistochemistry as single cells in conventional adenocarcinoma. NED of PC correlates with poor prognosis and tumor progression during androgen-deprivation therapy. The aim of our study was to correlate the expression of somatostatin receptor (SSTR) 1, 2, 3, 4, 5 subtypes in primary PC with NED pattern and Overall Survival (OS). Methods. PC tissues were reviewed from 100 pts who had undergone biopsy or radical prostatectomy for previously untreated advanced or metastatic PC from 2002 to 2007. 24 samples expressed hystologically chromogranin A (CgA), a marker of NED expression. Patient characteristics included: median age 68 years (range 45–83), median baseline PSA: 70 ng/ml (range 0.3–200), median ECOG Performance Status: 1 (range 0–2), Gleason score ≥ 7, medium serum level of CgA was 56.2 nmol/L (range 0.5–120). Results: The expression of SSTR subtypes (1, 2, 3, 4, 5) were investigated and our data identified four histological features. SSTR1 was expressed in 4/24 samples, SSTR 5 was detected in 2/24 samples, both SSTR1 and SSTR5 were found in 6/24 samples. OS at last follow up on July 2008 was 60%. SSTR 1–5 were undetectable in 12/24 pts with more aggressive clinical course and the OS was < 10%. The PSA and CgA levels were not correlated with clinical outcome. SSTR subtypes 2, 3 an 4 were not expressed in all 24 samples. Conclusions: SSTRs expression significantly correlated with OS. The absence of SSTR 1 and 5 in more aggressive disease could represent a growth advantage in NED prostate cancer. SSTRs and somatostatin analogs are potential targets for prostate cancer treatment. No significant financial relationships to disclose.

Molecular imaging of neuroendocrine differentiation of prostate cancer: a case series

2021 ◽  
Author(s):  
Amir Iravani ◽  
Catherine Mitchell ◽  
Tim Akhurst ◽  
Shahneen Sandhu ◽  
Michael S. Hofman ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Molecular Imaging ◽  
Case Series ◽  
Neuroendocrine Differentiation

scholarly journals New Frontiers in Molecular Imaging Using Peptide-Based Radiopharmaceuticals for Prostate Cancer

2020 ◽  
Vol 8 ◽  
Author(s):  
Xin Li ◽  
Huawei Cai ◽  
Xiaoai Wu ◽  
Li Li ◽  
Haoxing Wu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Computed Tomography ◽  
Molecular Imaging ◽  
Somatostatin Receptor ◽  
Photon Emission ◽  
Molecular Medicine ◽  
Emission Computed Tomography ◽  
Radiolabeled Peptides ◽  
Peptide Receptor ◽  
Emission Computed

The high incidence of prostate cancer (PCa) increases the need for progress in its diagnosis, staging, and precise treatment. The overexpression of tumor-specific receptors for peptides in human cancer cells, such as gastrin-releasing peptide receptor, natriuretic peptide receptor, and somatostatin receptor, has indicated the ideal molecular basis for targeted imaging and therapy. Targeting these receptors using radiolabeled peptides and analogs have been an essential topic on the current forefront of PCa studies. Radiolabeled peptides have been used to target receptors for molecular imaging in human PCa with high affinity and specificity. The radiolabeled peptides enable optimal quick elimination from blood and normal tissues, producing high contrast for positron emission computed tomography and single-photon emission computed tomography imaging with high tumor-to-normal tissue uptake ratios. Owing to their successful application in visualization, peptide derivatives with therapeutic radionuclides for peptide receptor radionuclide therapy in PCa have been explored in recent years. These developments offer the promise of personalized, molecular medicine for individual patients. Hence, we review the preclinical and clinical literature in the past 20 years and focus on the newer developments of peptide-based radiopharmaceuticals for the imaging and therapy of PCa.

Molecular Imaging in Neuroendocrine Differentiation of Prostate Cancer

2017 ◽  
Vol 42 (5) ◽  
pp. 410-413 ◽  
Author(s):  
Sharjeel Usmani ◽  
Najeeb Ahmed ◽  
Fahad Marafi ◽  
Rashid Rasheed ◽  
Henney G. Amanguno ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Molecular Imaging ◽  
Neuroendocrine Differentiation

scholarly journals Increased Expression of AKT3 in Neuroendocrine Differentiated Prostate Cancer Cells Alters the Response Towards Anti-Androgen Treatment

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 578
Author(s):  
Marc Wiesehöfer ◽  
Elena Dilara Czyrnik ◽  
Martin Spahn ◽  
Saskia Ting ◽  
Henning Reis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Target Genes ◽  
Neuroendocrine Differentiation ◽  
Marker Genes ◽  
Castration Resistant Prostate Cancer ◽  
Lncap Cells ◽  
Prostate Cancer Cells ◽  
Neuroendocrine Prostate Cancer ◽  
Long Term Treatment

Patients with advanced prostate carcinoma are often treated with an androgen deprivation therapy but long-term treatment can result in a metastatic castration-resistant prostate cancer. This is a more aggressive, untreatable tumor recurrence often containing areas of neuroendocrine differentiated prostate cancer cells. Using an in vitro model of NE-like cancer cells, it could previously be shown that neuroendocrine differentiation of LNCaP cells leads to a strong deregulation of mRNA and miRNA expression. We observe elevated RNA and protein levels of AKT Serine/Threonine Kinase 3 (AKT3) in neuroendocrine-like LNCaP cells. We used prostate resections from patients with neuroendocrine prostate cancer to validate these results and detect a co-localization of neuroendocrine marker genes with AKT3. Analysis of downstream target genes FOXO3A and GSK3 strengthens the assumption AKT3 may play a role in neuroendocrine differentiation. Overexpression of AKT3 shows an increased survival rate of LNCaP cells after apoptosis induction, which in turn reflects the significance in vivo or for treatment. Furthermore, miR-17, −20b and −106b, which are decreased in neuroendocrine-like LNCaP cells, negatively regulate AKT3 biosynthesis. Our findings demonstrate AKT3 as a potential therapeutic target and diagnostic tool in advanced neuroendocrine prostate cancer and a new mRNA–miRNA interaction with a potential role in neuroendocrine differentiation of prostate cancer.

Molecular imaging with 64Cu-PSMA PET/CT in Theranostics of prostate cancer

2016 ◽  
Author(s):  
Aviral Singh ◽  
Harshad Kulkarni ◽  
Richard P. Baum
Keyword(s):  
Prostate Cancer ◽  
Molecular Imaging ◽  
Psma Pet ◽  
Pet Ct
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