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Special Issue "PSMA in Prostate Cancer"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (30 September 2021).

Special Issue Editor

Dr. Finn Edler von Eyben
E-Mail Website
Guest Editor
Center of Tobacco Control Research, Odense, Denmark
Interests: cancer biology; urologic oncology; tumor markers
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Prostate Cancer has the second highest mortality for men in Western Societies. Prostate Specific Membrane Antigen (PSMA) is a glycoprotein that is highly expressed in plasma membrane of prostate cancer especially in the most aggressive forms for prostate cancer. In the recent decade PSMA PET/CT has become widely used in diagnostics of patients with metastatic castration-resistant prostate cancer (mCRPC). PSMA PET/CT has a high detection rate even for patients with low values of prostate specific antigen (PSA). Staging with PSMA PET/CT change planned treatment for more than a quarter of the patients. Radioligands can bind to the extracellular part of PSMA. Thereby the radioligand is absorbed into the cancer cells and damage the DNA of the cells. PSMA radioligand therapy is a safe and effective treatment of patients with metastatic castration-resistant prostate cancer as documented in two published randomized controlled trials, the TheraP and VISION trials. This issue of International Journal of Molecular Sciences provides up-to-date information on the use of PSMA for diagnostics and treatment of patients with prostate cancer. The issue serves as a very useful resource tool for patients, physicians, and researchers dealing with the challenge of mCRPC.

This issue has a joint special issue (https://0-www-mdpi-com.brum.beds.ac.uk/journal/diagnostics/special_issues/PSMA_diag) with our sister journal /Diagnostics/ (ISSN 2075-4418, IF: 3.110, https://0-www-mdpi-com.brum.beds.ac.uk/journal/diagnostics). For papers focused on molecular science are encouraged to submit to IJMS, for others to Diagnostics.

Dr. Finn Edler von Eyben
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • prospective studies
  • prostate cancer
  • retrospective studies
  • reviews
  • tumor biology
  • theranostics

Published Papers (3 papers)

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Research

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Communication
Enzalutamide Enhances PSMA Expression of PSMA-Low Prostate Cancer
Int. J. Mol. Sci. 2021, 22(14), 7431; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147431 - 11 Jul 2021
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Abstract
Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) prolongs overall survival in men with metastatic castration-resistant prostate cancer (mCRPC). However, men with low PSMA expression are excluded from RLT. We explored the effect of androgen receptor blockade with enzalutamide on PSMA expression. Assessment of [...] Read more.
Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) prolongs overall survival in men with metastatic castration-resistant prostate cancer (mCRPC). However, men with low PSMA expression are excluded from RLT. We explored the effect of androgen receptor blockade with enzalutamide on PSMA expression. Assessment of PSMA and androgen receptor (AR) expression on the human PC cell lines 22Rv1, C4-2, and LNCaP by immunohistochemistry and flow cytometry revealed low (22Rv1) and high (C4-2 and LNCaP) PSMA expression, and high, comparable AR positivity. Treatment with enzalutamide increased PSMA levels in 22Rv1, C4-2, and LNCaP (2.2/2.3/2.6-fold, p = 0.0005/0.03/0.046) after one week compared to DMSO-treated controls as assessed by flow cytometry. NOD/Scid mice bearing 22Rv1 tumors were treated with enzalutamide for two weeks. Positron emission tomography/computed tomography (PET/CT) demonstrated higher tumor uptake of 68Ga-PSMA after enzalutamide treatment (p = 0.004). Similarly, a clinical case with low baseline PSMA avidity demonstrated increased uptake of 68Ga-PSMA after enzalutamide on PET/CT and post-therapeutic 177Lu-PSMA scintigraphy in a patient with mCRPC. Enzalutamide induced PSMA expression in the 22Rv1 xenograft model and in an mCRPC patient, both with low baseline tumoral PSMA levels. Therefore, enzalutamide pre-treatment might render patients with low PSMA expression eligible for 177Lu-PSMA RLT. Full article
(This article belongs to the Special Issue PSMA in Prostate Cancer)
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Article
Evaluation of the PSMA-Binding Ligand 212Pb-NG001 in Multicellular Tumour Spheroid and Mouse Models of Prostate Cancer
Int. J. Mol. Sci. 2021, 22(9), 4815; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094815 - 01 May 2021
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Abstract
Radioligand therapy targeting the prostate-specific membrane antigen (PSMA) is rapidly evolving as a promising treatment for metastatic castration-resistant prostate cancer. The PSMA-targeting ligand p-SCN-Bn-TCMC-PSMA (NG001) labelled with 212Pb efficiently targets PSMA-positive cells in vitro and in vivo. The aim of this preclinical [...] Read more.
Radioligand therapy targeting the prostate-specific membrane antigen (PSMA) is rapidly evolving as a promising treatment for metastatic castration-resistant prostate cancer. The PSMA-targeting ligand p-SCN-Bn-TCMC-PSMA (NG001) labelled with 212Pb efficiently targets PSMA-positive cells in vitro and in vivo. The aim of this preclinical study was to evaluate the therapeutic potential of 212Pb-NG001 in multicellular tumour spheroid and mouse models of prostate cancer. The cytotoxic effect of 212Pb-NG001 was tested in human prostate C4-2 spheroids. Biodistribution at various time points and therapeutic effects of different activities of the radioligand were investigated in male athymic nude mice bearing C4-2 tumours, while long-term toxicity was studied in immunocompetent BALB/c mice. The radioligand induced a selective cytotoxic effect in spheroids at activity concentrations of 3–10 kBq/mL. In mice, the radioligand accumulated rapidly in tumours and was retained over 24 h, while it rapidly cleared from nontargeted tissues. Treatment with 0.25, 0.30 or 0.40 MBq of 212Pb-NG001 significantly inhibited tumour growth and improved median survival with therapeutic indexes of 1.5, 2.3 and 2.7, respectively. In BALB/c mice, no signs of long-term radiation toxicity were observed at activities of 0.05 and 0.33 MBq. The obtained results warrant clinical studies to evaluate the biodistribution, therapeutic efficacy and toxicity of 212Pb-NG001. Full article
(This article belongs to the Special Issue PSMA in Prostate Cancer)
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Review

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Review
Optimizing PSMA Radioligand Therapy for Patients with Metastatic Castration-Resistant Prostate Cancer. A Systematic Review and Meta-Analysis
Int. J. Mol. Sci. 2020, 21(23), 9054; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21239054 - 28 Nov 2020
Cited by 10 | Viewed by 1080
Abstract
The aim of the review was to evaluate patient and treatment characteristics for patients with metastatic castration-resistant prostate cancer (mCRPC) treated with PSMA radioligand therapy (PRLT) associated with above-average outcome. The systematic review and meta-analysis followed recommendations by the Preferred Reporting Items for [...] Read more.
The aim of the review was to evaluate patient and treatment characteristics for patients with metastatic castration-resistant prostate cancer (mCRPC) treated with PSMA radioligand therapy (PRLT) associated with above-average outcome. The systematic review and meta-analysis followed recommendations by the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA). We searched for publications in PubMed, Embase, and ClinicalTrials.gov up to 31 September 2020. Thirty-six publications and four duplicates reported 2346 patients. Nearly two-thirds of the patients had bone metastases. Median overall survival (OS) was 16 months. Asymptomatic patients and patients with only lymph node metastases lived longer than symptomatic patients and patients with more extensive metastases. Patients treated with an intensified schedule of 177Lu PRLT lived longer than those treated with a conventional schedule. Half of the patients obtained a PSA decline ≥ 50% and these patients lived longer than those with less PSA decline. Approximately 10% of the patients developed hematologic toxicity with anemia grade 3 as the most severe adverse effect. Characteristics for patients, cancer, restaging, and PRLT predict above average overall survival following treatment with PRLT. Full article
(This article belongs to the Special Issue PSMA in Prostate Cancer)
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