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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

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 (31 July 2021) | Viewed by 12695

Special Issue Editors

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
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

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 as 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) 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 an accurate pre-treatment patients’ selection and outcome prediction.

The aim of this Special Issue is to solicit original researches 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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Keywords

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

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Published Papers (3 papers)

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Research

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26 pages, 4115 KiB  
Article
Design and Evaluation of 223Ra-Labeled and Anti-PSMA Targeted NaA Nanozeolites for Prostate Cancer Therapy—Part II. Toxicity, Pharmacokinetics and Biodistribution
by Anna Lankoff, Malwina Czerwińska, Rafał Walczak, Urszula Karczmarczyk, Kamil Tomczyk, Kamil Brzóska, Giulio Fracasso, Piotr Garnuszek, Renata Mikołajczak and Marcin Kruszewski
Int. J. Mol. Sci. 2021, 22(11), 5702; https://doi.org/10.3390/ijms22115702 - 27 May 2021
Cited by 12 | Viewed by 3184
Abstract
Metastatic castration-resistant prostate cancer (mCRPC) is a progressive and incurable disease with poor prognosis for patients. Despite introduction of novel therapies, the mortality rate remains high. An attractive alternative for extension of the life of mCRPC patients is PSMA-based targeted radioimmunotherapy. In this [...] Read more.
Metastatic castration-resistant prostate cancer (mCRPC) is a progressive and incurable disease with poor prognosis for patients. Despite introduction of novel therapies, the mortality rate remains high. An attractive alternative for extension of the life of mCRPC patients is PSMA-based targeted radioimmunotherapy. In this paper, we extended our in vitro study of 223Ra-labeled and PSMA-targeted NaA nanozeolites [223RaA-silane-PEG-D2B] by undertaking comprehensive preclinical in vitro and in vivo research. The toxicity of the new compound was evaluated in LNCaP C4-2, DU-145, RWPE-1 and HPrEC prostate cells and in BALB/c mice. The tissue distribution of 133Ba- and 223Ra-labeled conjugates was studied at different time points after injection in BALB/c and LNCaP C4-2 tumor-bearing BALB/c Nude mice. No obvious symptoms of antibody-free and antibody-functionalized nanocarriers cytotoxicity and immunotoxicity was found, while exposure to 223Ra-labeled conjugates resulted in bone marrow fibrosis, decreased the number of WBC and platelets and elevated serum concentrations of ALT and AST enzymes. Biodistribution studies revealed high accumulation of 223Ra-labeled conjugates in the liver, lungs, spleen and bone tissue. Nontargeted and PSMA-targeted radioconjugates exhibited a similar, marginal uptake in tumour lesions. In conclusion, despite the fact that NaA nanozeolites are safe carriers, the intravenous administration of NaA nanozeolite-based radioconjugates is dubious due to its high accumulation in the lungs, liver, spleen and bones. Full article
(This article belongs to the Special Issue Prostate Cancer: From Molecular Imaging to Immunological and Target Therapies)
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35 pages, 17698 KiB  
Article
PSMA-D4 Radioligand for Targeted Therapy of Prostate Cancer: Synthesis, Characteristics and Preliminary Assessment of Biological Properties
by Piotr Garnuszek, Urszula Karczmarczyk, Michał Maurin, Arkadiusz Sikora, Jolanta Zaborniak, Justyna Pijarowska-Kruszyna, Antoni Jaroń, Monika Wyczółkowska, Wioletta Wojdowska, Dariusz Pawlak, Piotr F. J. Lipiński and Renata Mikołajczak
Int. J. Mol. Sci. 2021, 22(5), 2731; https://doi.org/10.3390/ijms22052731 - 8 Mar 2021
Cited by 9 | Viewed by 4457
Abstract
A new PSMA ligand (PSMA-D4) containing the Glu-CO-Lys pharmacophore connected with a new linker system (L-Trp-4-Amc) and chelator DOTA was developed for radiolabeling with therapeutic radionuclides. Herein we describe the synthesis, radiolabeling, and preliminary biological evaluation of the novel PSMA-D4 ligand. Synthesized PSMA-D4 [...] Read more.
A new PSMA ligand (PSMA-D4) containing the Glu-CO-Lys pharmacophore connected with a new linker system (L-Trp-4-Amc) and chelator DOTA was developed for radiolabeling with therapeutic radionuclides. Herein we describe the synthesis, radiolabeling, and preliminary biological evaluation of the novel PSMA-D4 ligand. Synthesized PSMA-D4 was characterized using TOF-ESI-MS, NMR, and HPLC methods. The novel compound was subject to molecular modeling with GCP-II to compare its binding mode to analogous reference compounds. The radiolabeling efficiency of PSMA-D4 with 177Lu, 90Y, 47Sc, and 225Ac was chromatographically tested. In vitro studies were carried out in PSMA-positive LNCaP tumor cells membranes. The ex vivo tissue distribution profile of the radioligands and Cerenkov luminescence imaging (CLI) was studied in LNCaP tumor-bearing mice. PSMA-D4 was synthesized in 24% yield and purity >97%. The radio complexes were obtained with high yields (>97%) and molar activity ranging from 0.11 to 17.2 GBq mcmol−1, depending on the radionuclide. In vitro assays confirmed high specific binding and affinity for all radiocomplexes. Biodistribution and imaging studies revealed high accumulation in LNCaP tumor xenografts and rapid clearance of radiocomplexes from blood and non-target tissues. These render PSMA-D4 a promising ligand for targeted therapy of prostate cancer (PCa) metastases. Full article
(This article belongs to the Special Issue Prostate Cancer: From Molecular Imaging to Immunological and Target Therapies)
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Review

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26 pages, 3522 KiB  
Review
Prognostic and Theranostic Applications of Positron Emission Tomography for a Personalized Approach to Metastatic Castration-Resistant Prostate Cancer
by Luca Filippi, Viviana Frantellizzi, Agostino Chiaravalloti, Mariano Pontico, Maria Silvia De Feo, Ferdinando Corica, Melissa Montebello, Orazio Schillaci, Giuseppe De Vincentis and Oreste Bagni
Int. J. Mol. Sci. 2021, 22(6), 3036; https://doi.org/10.3390/ijms22063036 - 16 Mar 2021
Cited by 12 | Viewed by 4172
Abstract
Metastatic castration-resistant prostate cancer (mCRPC) represents a condition of progressive disease in spite of androgen deprivation therapy (ADT), with a broad spectrum of manifestations ranging from no symptoms to severe debilitation due to bone or visceral metastatization. The management of mCRPC has been [...] Read more.
Metastatic castration-resistant prostate cancer (mCRPC) represents a condition of progressive disease in spite of androgen deprivation therapy (ADT), with a broad spectrum of manifestations ranging from no symptoms to severe debilitation due to bone or visceral metastatization. The management of mCRPC has been profoundly modified by introducing novel therapeutic tools such as antiandrogen drugs (i.e., abiraterone acetate and enzalutamide), immunotherapy through sipuleucel-T, and targeted alpha therapy (TAT). This variety of approaches calls for unmet need of biomarkers suitable for patients’ pre-treatment selection and prognostic stratification. In this scenario, imaging with positron emission computed tomography (PET/CT) presents great and still unexplored potential to detect specific molecular and metabolic signatures, some of whom, such as the prostate specific membrane antigen (PSMA), can also be exploited as therapeutic targets, thus combining diagnosis and therapy in the so-called “theranostic” approach. In this review, we performed a web-based and desktop literature research to investigate the prognostic and theranostic potential of several PET imaging probes, such as 18F-FDG, 18F-choline and 68Ga-PSMA-11, also covering the emerging tracers still in a pre-clinical phase (e.g., PARP-inhibitors’ analogs and the radioligands binding to gastrin releasing peptide receptors/GRPR), highlighting their potential for defining personalized care pathways in mCRPC Full article
(This article belongs to the Special Issue Prostate Cancer: From Molecular Imaging to Immunological and Target Therapies)
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