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

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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 19207

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Dr. Agostino Chiaravalloti

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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
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Prof. Dr. Luca Filippi

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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

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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

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Keywords

prostate cancer
molecular imaging
targeted therapy
PSMA
theranostics

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Published Papers (6 papers)

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Editorial

Jump to: Research, Review

3 pages, 169 KiB

Open AccessEditorial

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 1348

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

Open AccessEditor’s ChoiceArticle

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 2889

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 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

Open AccessArticle

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 14 | Viewed by 3338

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 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 SUV_peak/max and the imaging-based response to [⁶⁸Ga]Ga-PSMA-11 PET/CT (most avid lesion SUV_peak/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 SUV_peak 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 SUV_peak/max in men with mCRPC receiving two cycles of [¹⁷⁷Lu]Lu-PSMA-617 treatment. The SUV_peak 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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Figure 1

Figure 1
Flow-chart of the retrospective included patients. Full article ">Figure 2
Example of two patients: responder and non-responder after two cycles of [177Lu]Lu-PSMA-617 treatment. (a): Responder (TL-PSMA reduction 95.01%, PSA-reduction: 99.5%): 78-year-old men with a Gleason score of nine, a ECOG performance score zero and a SUVpeak of the most avid lesion of 17.7. Activity first cycle [177Lu]Lu-PSMA-617: 6.3 GBq, activity second cycle [177Lu]Lu-PSMA-617: 6.3 GBq. TL-PSMA pre-treatment: 1961.02 SUVlbm,peak*cm3, TL-PSMA post-treatment: 97.79 SUVlbm,peak*cm3. (b): Non-responder (TL-PSMA increase: 750.77%, PSA-increase: 566.7%): 69-year-old men with a Gleason score of eight, a ECOG performance score of two and a SUVpeak of the most avid lesion of 9.48. Activity first cycle [177Lu]Lu-PSMA-617: 6.2 GBq, activity second cycle [177Lu]Lu-PSMA-617: 6.2GBq. TL-PSMA pre-treatment: 260.58 SUVlbm,peak*cm3, TL-PSMA post-treatment: 2216.94 SUVlbm,peak*cm3. Full article ">Figure 3
Receiver Operating Characteristics-curves for the predicting of imaging-based response including bootstrap-corrected c-statistic of the three separately tested models in logistic regression. (a): SUVpeak all measured lesions together, (b): SUVpeak lymph node metastases, (c): SUVpeak bone metastases. Legend: AUC = Area under the curve, SUV = Standardized uptake value. Full article ">Figure 4
SUVpeak values per response category on the tumor-level. Legend: iCR = Imaging complete response, iPD = Imaging progression disease, iPR = Imaging partial response, iSD = Imaging stable disease, SUV = Standardized uptake value. Full article ">Figure 5
Relationship between metastasis type, response, and accumulation. Numbers in the plot indicate the number of tumors in the corresponding group. Legend: iCR = Imaging complete response, iPD = Imaging progression disease, iPR = Imaging partial response, iSD = Imaging stable disease, SUV = Standardized uptake value. Full article ">Figure 6
Kaplan–Meier curves showing the significant survival probability, expressed as a percentage, following the first cycle of [177Lu]Lu-PSMA-617 treatment. (a): ECOG performance score, (b): Primary prostate in situ yes or no, (c): Imaging-based response (≥30 TL-PSMA reduction) yes or no, (d): Biochemical response (>50% PSA reduction) yes or no. Legend: ECOG = Eastern Cooperative Oncology Group. Full article ">

9 pages, 1066 KiB

Open AccessArticle

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 1994

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 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

Open AccessArticle

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 10 | Viewed by 4430

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 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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Figure 1

Figure 1
Diagnostic flow-chart for patient selection. Full article ">Figure 2
Graphic illustration of PET/CT detection rate in enrolled patients, stratified into 4 groups according to discrete PSA intervals. Full article ">Figure 3
ROC curve analysis shows the accuracy of the PSA level (A) and PSA doubling time (B), measured prior to 18F-FACBC PET/CT scan, for predicting positive results. Full article ">Figure 4
Box plot graph showing the PSA level distribution in patients with positive (A) and negative (B) 18F-FABC PET/CT scans, 2-tailed t-test results were significant at p = 0.005. The 2 hot dots in panel A represent 2 subjects with PSA value strongly out of range (i.e., 5 and 7.8 ng/mL, respectively). Full article ">Figure 5
Graph illustration of the therapeutic changes determined by 18F-FACBC PET/CT in patients classified according to modified PROMISE reading approach. Full article ">Figure 6
A 72-year-old patient 6 years post prostatectomy for pT3b pN0 ISUP Grade Group 4 prostate adenocarcinoma, presenting biochemical recurrence with PSA level prior to PET/CT of 0.38 ng/mL. (A) MIP image showing an area of increased tracer incorporation in the right pelvis (arrow). Fused corresponding PET/CT axial (B, arrow) and coronal (C, arrow) slices depicting a round-shaped right obturator lymph node, characterized by 18F-FACBC pathological uptake, with a maximum diameter of 12 mm and a maximum standardized uptake value (SUVmax) of 7.7, superior to bone marrow SUVmean (3.1). Final diagnosis was T0N1M0 according to PROMISE. Intended therapy prior to PET/CT was androgen deprivation therapy, after the collegial discussion of 18F-FACBC PET/CT’s results, the patient was submitted to stereotactic radiotherapy with PSA response. Full article ">Figure 7
A 74-year-old patient 5 years post radiotherapy for cT2b ISUP Grade Group 4 prostate adenocarcinoma, presenting biochemical recurrence with PSA level prior to PET/CT of 1.25 ng/mL. (A) MIP image showing an area of increased tracer incorporation in the left umbilical region (arrow). Fused corresponding PET/CT axial (B, arrow) and coronal (C, arrow) slices depicting a round-shaped para-aortic lymph node, located below the left kidney artery, characterized by 18F-FACBC pathological uptake, with a maximum diameter of 14 mm and a maximum standardized uptake value (SUVmax) of 10.1, superior to bone marrow SUVmean (3.3). Final diagnosis was T0N0M1a according to PROMISE. Intended therapy prior to PET/CT was androgen deprivation therapy, after the collegial discussion of 18F-FACBC PET/CT’s results, the patient was submitted to stereotactic radiotherapy on the abdominal node with PSA response. Full article ">

Review

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23 pages, 1407 KiB

Open AccessReview

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 16 | Viewed by 4092

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 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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