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Prostate Cancer: from Molecular Imaging to Immunological and Target Therapies...
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Prostate Cancer: from Molecular Imaging to Immunological and Target Therapies II

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 17577

Special Issue Editors

Dr. Agostino Chiaravalloti

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Guest Editor
Department of Biomedicine and Prevention, University Tor Vergata, Rome, Italy
Interests: molecular imaging; oncology; PET/CT; neurodegenerative disorders; neuroimaging; Alzheimer's disease; brain tumors; pediatric tumors
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Luca Filippi

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Guest Editor
Nuclear Medicine Unit, Santa Maria Goretti Hospital, viale Canova snc, 04100 Latina, Italy
Interests: FDG PET/CT; oncology; therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Prostate cancer (PC) represents a crucial public health issue in Western countries. For many years, chemotherapy with taxanes has represented the only option for PC progressing in spite of castrate levels of testosterone, a severe clinical condition termed metastatic castration-resistant prostate cancer (mCRPC). The management of mCRPC has been deeply modified by the introduction of several novel treatments, such as second-generation antiandrogens, PARP (poly(ADP)-ribose polymerase) inhibitors, and cellular immunotherapy. Furthermore, targeted radionuclide therapy with the bone-seeking agent radium-223 dichloride (Xofigo) has proved useful for improving survival in mCRPC with bone metastases. More recently, prostate-specific membrane antigen (PSMA) has emerged as an attractive biomarker both for positron emission tomography (PET) imaging and targeted radionuclide therapy, in the perspective of combining diagnosis and treatment in a unique approach (i.e., “theranostics”). The aforementioned emerging therapeutic options call for an unmet need of imaging/molecular biomarkers, suitable for accurate pre-treatment patient selection and outcome prediction.

The aim of this Special Issue is to solicit original research or review articles highlighting the potential usefulness of different molecular probes (18F/11C-choline, 18F-fluciclovine, PSMA-targeting agents, 18F-fluoride, PARP-inhibitors’ analogues) in order to define customized therapeutic pathways in patients affected by PC.

Dr. Agostino Chiaravalloti
Dr. Luca Filippi
Guest Editors

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. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • prostate cancer
  • molecular imaging
  • targeted therapy
  • PSMA
  • theranostics

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Published Papers (6 papers)

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Editorial

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3 pages, 169 KiB  
Editorial
Prostate Cancer: From Molecular Imaging to Immunological and Target Therapies
by Luca Filippi and Agostino Chiaravalloti
Biomedicines 2023, 11(4), 1176; https://doi.org/10.3390/biomedicines11041176 - 14 Apr 2023
Viewed by 1228
Abstract
Prostate cancer (PCa) is one of the most common malignancies and a leading cause of cancer-related deaths, affecting a million people worldwide with a particularly high burden in countries with a low human development index [...] Full article
(This article belongs to the Special Issue Prostate Cancer: from Molecular Imaging to Immunological and Target Therapies II)

Research

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12 pages, 1958 KiB  
Article
The Role of [18F]F-Choline PET/CT in the Initial Management and Outcome Prediction of Prostate Cancer: A Real-World Experience from a Multidisciplinary Approach
by Luca Urso, Giovanni Christian Rocca, Francesca Borgia, Federica Lancia, Antonio Malorgio, Mauro Gagliano, Mauro Zanetto, Licia Uccelli, Corrado Cittanti, Carmelo Ippolito, Laura Evangelista and Mirco Bartolomei
Biomedicines 2022, 10(10), 2463; https://doi.org/10.3390/biomedicines10102463 - 1 Oct 2022
Cited by 8 | Viewed by 2531
Abstract
Initial staging of prostate cancer (PCa) is usually performed with conventional imaging (CI), involving computed tomography (CT) and bone scanning (BS). The aim of this study was to analyze the role of [18F]F-choline positron emission tomography (PET)/CT in the initial management [...] Read more.
Initial staging of prostate cancer (PCa) is usually performed with conventional imaging (CI), involving computed tomography (CT) and bone scanning (BS). The aim of this study was to analyze the role of [18F]F-choline positron emission tomography (PET)/CT in the initial management and outcome prediction of PCa patients by analyzing data from a multidisciplinary approach. We retrospectively analyzed 82 patients who were discussed by the uro-oncology board of the University Hospital of Ferrara for primary staging newly diagnosed PCa (median age 72 (56–86) years; median baseline prostate specific antigen (PSA) equal to 8.73 ng/mL). Patients were divided into three groups based on the imaging performed: group A = only CI; group B = CI + [18F]F-choline PET/CT; group C = only [18F]F-choline PET/CT. All data on imaging findings, therapy decisions and patient outcomes were retrieved from hospital information systems. Moreover, we performed a sub-analysis of semiquantitative parameters extracted from [18F]F-choline PET/CT to search any correlation with patient outcomes. The number of patients included in each group was 35, 35 and 12, respectively. Patients with higher values of initial PSA were subjected to CI + PET/CT (p = 0.005). Moreover, the use of [18F]F-choline PET/CT was more frequent in patients with higher Gleason score (GS) or ISUP grade (p = 0.013). The type of treatment performed (surgery n = 33; radiation therapy n = 22; surveillance n = 6; multimodality therapy n = 6; systemic therapy n = 13; not available n = 2) did not show any relationship with the modality adopted to stage the disease. [18F]F-choline PET/CT induced a change of planned therapy in 5/35 patients in group B (14.3%). Moreover, patients investigated with [18F]F-choline PET/CT alone demonstrated longer biochemical recurrence (BCR)-free survival (30.8 months) in comparison to patients of groups A and B (15.5 and 23.5 months, respectively, p = 0.006), probably due to a more accurate selection of primary treatment. Finally, total lesion choline kinase activity (TLCKA) of the primary lesion, calculated by multiplying metabolic tumor volume and mean standardized uptake value (SUVmean), was able to more effectively discriminate patients who had recurrence after therapy compared to those without (p = 0.03). In our real-world experience [18F]F-choline PET/CT as a tool for the initial management of PCa had a relevant impact in terms of therapy selection and was associated with longer BCR-free survival. Moreover, TLCKA of the primary lesion looks a promising parameter for predicting recurrence after curative therapy. Full article
(This article belongs to the Special Issue Prostate Cancer: from Molecular Imaging to Immunological and Target Therapies II)
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16 pages, 2487 KiB  
Article
Baseline Imaging Derived Predictive Factors of Response Following [177Lu]Lu-PSMA-617 Therapy in Salvage Metastatic Castration-Resistant Prostate Cancer: A Lesion- and Patient-Based Analysis
by Esmée C. A. van der Sar, Adinda J. S. Kühr, Sander C. Ebbers, Andrew M. Henderson, Bart de Keizer, Marnix G. E. H. Lam and Arthur J. A. T. Braat
Biomedicines 2022, 10(7), 1575; https://doi.org/10.3390/biomedicines10071575 - 1 Jul 2022
Cited by 12 | Viewed by 3082
Abstract
Earlier studies have mostly identified pre-therapeutic clinical and laboratory parameters for the prediction of treatment response to [177Lu]Lu-PSMA-617 in metastatic castration resistant prostate cancer patients (mCRPC). The current study investigated whether imaging-derived factors on baseline [68Ga]Ga-PSMA-11 PET/CT can potentially [...] Read more.
Earlier studies have mostly identified pre-therapeutic clinical and laboratory parameters for the prediction of treatment response to [177Lu]Lu-PSMA-617 in metastatic castration resistant prostate cancer patients (mCRPC). The current study investigated whether imaging-derived factors on baseline [68Ga]Ga-PSMA-11 PET/CT can potentially predict the response after two cycles of [177Lu]Lu-PSMA-617 treatment, in a lesion- and patient-based analysis in men with mCRPC. Included patients had histologically proven mCRPC and a [68Ga]Ga-PSMA-11 PET/CT before and after two cycles of [177Lu]Lu-PSMA-617 treatment. The imaging-based response was evaluated on lesion-level (standardized uptake value (SUV) reduction) and patient-level (total lesion PSMA (TL-PSMA) reduction). In the lesion-level analysis, a clear relationship was found between SUVpeak/max and the imaging-based response to [68Ga]Ga-PSMA-11 PET/CT (most avid lesion SUVpeak/max ≥ 30% reduction) (p < 0.001), with no significant difference in cut-off values between different sites of metastases (i.e., lymph node, bone or visceral metastasis). In patient-level analysis, baseline PSA and SUVpeak values of most avid metastasis were significantly associated with imaging-based response (TL-PSMA ≥ 30% reduction) (p = 0.019 and p = 0.015). In pre-treatment with [68Ga]Ga-PSMA-11 PET/CT, a clear accumulation-response relationship in lesion-level was found for SUVpeak/max in men with mCRPC receiving two cycles of [177Lu]Lu-PSMA-617 treatment. The SUVpeak of the most avid lesion was the only image-derived factor predictive of the imaging-based response at the patient-level. Full article
(This article belongs to the Special Issue Prostate Cancer: from Molecular Imaging to Immunological and Target Therapies II)
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9 pages, 1066 KiB  
Article
68Ga-PSMA-11 PET/CT Initial Staging in Black and White South African Males with ISUP Grade Group 1 and 2 Prostate Adenocarcinoma
by Letjie C. Maserumule, Kgomotso M. G. Mokoala, Christophe van de Wiele, Gbenga Popoola, Khanyisile N. Hlongwa, Honest Ndlovu, Alex Maes, Mariza Vorster and Mike M. Sathekge
Biomedicines 2022, 10(4), 882; https://doi.org/10.3390/biomedicines10040882 - 12 Apr 2022
Cited by 2 | Viewed by 1855
Abstract
Prostate adenocarcinoma (PCa) is a leading cause of mortality. Black males with high-risk PCa have a poorer prognosis compared to white males. Patients with International Society of Urological Pathology (ISUP) Grade Group (GG) 1 and 2 PCa have little potential for metastases post [...] Read more.
Prostate adenocarcinoma (PCa) is a leading cause of mortality. Black males with high-risk PCa have a poorer prognosis compared to white males. Patients with International Society of Urological Pathology (ISUP) Grade Group (GG) 1 and 2 PCa have little potential for metastases post radical prostatectomy. 68Gallium prostate specific membrane antigen (68Ga-PSMA) PET/CT imaging for metastatic PCa is superior to conventional imaging in staging high-risk PCa. No strong evidence is available to support imaging low-risk patients. We aimed to evaluate the value of 68Ga-PSMA PET/CT in black and white South African (BSA and WSA) males with GG1 and 2 PCa at initial staging. We evaluated 25 WSA and 123 BSA males. The image findings were correlated with prostate specific antigen (PSA). PSA levels significantly correlated with both primary tumor and whole-body PSMA-tumor volume (PSMA-TV) and were higher in BSA males. No differences were noted in the occurrence of metastases; however, PSA, seminal vesicle invasion and black race predicted metastases. Our findings suggest higher PSMA expression and tumor burden in BSA with histologically low-risk PCa, and future research with immunohistochemistry evaluation will be essential to confirm these findings. Full article
(This article belongs to the Special Issue Prostate Cancer: from Molecular Imaging to Immunological and Target Therapies II)
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13 pages, 2354 KiB  
Article
Detection Rate and Clinical Impact of PET/CT with 18F-FACBC in Patients with Biochemical Recurrence of Prostate Cancer: A Retrospective Bicentric Study
by Luca Filippi, Oreste Bagni, Carmelo Crisafulli, Ivan Cerio, Gabriele Brunotti, Agostino Chiaravalloti, Orazio Schillaci and Franca Dore
Biomedicines 2022, 10(1), 177; https://doi.org/10.3390/biomedicines10010177 - 15 Jan 2022
Cited by 9 | Viewed by 4235
Abstract
Our aim was to assess the detection rate (DR) of positron emission computed tomography (PET/CT) with anti-1-amino-3-[18F]-flurocyclobutane-1-carboxylic acid (18F-FACBC) in patients with biochemical recurrence (BCR) from prostate cancer (PC). As a secondary endpoint, we evaluated 18F-FACBC PET/CT’s impact [...] Read more.
Our aim was to assess the detection rate (DR) of positron emission computed tomography (PET/CT) with anti-1-amino-3-[18F]-flurocyclobutane-1-carboxylic acid (18F-FACBC) in patients with biochemical recurrence (BCR) from prostate cancer (PC). As a secondary endpoint, we evaluated 18F-FACBC PET/CT’s impact on patients management. Clinical records of 81 patients submitted to 18F-FACBC PET/CT due to PC BCR in two Italian Nuclear Medicine Units were retrospectively assessed. DR was gauged in the whole cohort and stratifying patients by discrete intervals of PSA levels. PET/CT’s impact on clinical management was scored as (1) major if it entailed an intermodality change (e.g., from systemic to loco-regional therapy); (2) minor if it led to an intramodality change (e.g., modified radiotherapy field). PET/CT’s DR resulted in 76.9% in the whole cohort, with a positive predictive value of 96.7%. Stratified by PSA quartile intervals, PET/CT’s DR was 66.7%, 71.4%, 78.9% and 90% for PSA 0.2–0.57 ng/mL, 0.58–0.99 ng/mL, 1–1.5 ng/mL and >1.5 ng/mL without significant difference among groups (p = 0.81). The most common sites of relapse were prostate bed and pelvic lymph nodes (59.3%). PET/CT impacted on clinical management in 33/81 cases (40.7%), leading to a major change in 30 subjects (90.9%). 18F-FACBC PET/CT localized recurrence in patients with BCR, with meaningful DR also at low PSA levels and significantly impacted on clinical management. Full article
(This article belongs to the Special Issue Prostate Cancer: from Molecular Imaging to Immunological and Target Therapies II)
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Review

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23 pages, 1407 KiB  
Review
Pharmacological Optimization of PSMA-Based Radioligand Therapy
by Suzanne van der Gaag, Imke H. Bartelink, André N. Vis, George L. Burchell, Daniela E. Oprea-Lager and Harry Hendrikse
Biomedicines 2022, 10(12), 3020; https://doi.org/10.3390/biomedicines10123020 - 23 Nov 2022
Cited by 15 | Viewed by 3582
Abstract
Prostate cancer (PCa) is the most common malignancy in men of middle and older age. The standard treatment strategy for PCa ranges from active surveillance in low-grade, localized PCa to radical prostatectomy, external beam radiation therapy, hormonal treatment and chemotherapy. Recently, the use [...] Read more.
Prostate cancer (PCa) is the most common malignancy in men of middle and older age. The standard treatment strategy for PCa ranges from active surveillance in low-grade, localized PCa to radical prostatectomy, external beam radiation therapy, hormonal treatment and chemotherapy. Recently, the use of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) for metastatic castration-resistant PCa has been approved. PSMA is predominantly, but not exclusively, expressed on PCa cells. Because of its high expression in PCa, PSMA is a promising target for diagnostics and therapy. To understand the currently used RLT, knowledge about pharmacokinetics (PK) and pharmacodynamics (PD) of the PSMA ligand and the PSMA protein itself is crucial. PK and PD properties of the ligand and its target determine the duration and extent of the effect. Knowledge on the concentration–time profile, the target affinity and target abundance may help to predict the effect of RLT. Increased specific binding of radioligands to PSMA on PCa cells may be associated with better treatment response, where nonspecific binding may increase the risk of toxicity in healthy organs. Optimization of the radioligand, as well as synergistic effects of concomitant agents and an improved dosing strategy, may lead to more individualized treatment and better overall survival. Full article
(This article belongs to the Special Issue Prostate Cancer: from Molecular Imaging to Immunological and Target Therapies II)
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