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Search Results (1,040)

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26 pages, 1745 KiB  
Review
Emerging PET Imaging Agents and Targeted Radioligand Therapy: A Review of Clinical Applications and Trials
by Maierdan Palihati, Jeeban Paul Das, Randy Yeh and Kathleen Capaccione
Tomography 2025, 11(8), 83; https://doi.org/10.3390/tomography11080083 - 28 Jul 2025
Abstract
Targeted radioligand therapy (RLT) is an emerging field in anticancer therapeutics with great potential across tumor types and stages of disease. While much progress has focused on agents targeting somatostatin receptors and prostate-specific membrane antigen (PSMA), the same advanced radioconjugation methods and molecular [...] Read more.
Targeted radioligand therapy (RLT) is an emerging field in anticancer therapeutics with great potential across tumor types and stages of disease. While much progress has focused on agents targeting somatostatin receptors and prostate-specific membrane antigen (PSMA), the same advanced radioconjugation methods and molecular targeting have spurred the development of numerous theranostic combinations for other targets. A number of the most promising agents have progressed to clinical trials and are poised to change the landscape of positron emission tomography (PET) imaging. Here, we present recent data on some of the most important emerging molecular targeted agents with their exemplar clinical images, including agents targeting fibroblast activation protein (FAP), hypoxia markers, gastrin-releasing peptide receptors (GRPrs), and integrins. These radiopharmaceuticals share the promising characteristic of being able to image multiple types of cancer. Early clinical trials have already demonstrated superiority to 18F-fluorodeoxyglucose (18F-FDG) for some, suggesting the potential to supplant this longstanding PET radiotracer. Here, we provide a primer for practicing radiologists, particularly nuclear medicine clinicians, to understand novel PET imaging agents and their clinical applications, as well as the availability of companion targeted radiotherapeutics, the status of their regulatory approval, the potential challenges associated with their use, and the future opportunities and perspectives. Full article
(This article belongs to the Section Cancer Imaging)
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26 pages, 2997 KiB  
Review
PSMA-Directed Theranostics in Prostate Cancer
by Salman Ayub Jajja, Nandini Sodhi, Ephraim E. Parent and Parminder Singh
Biomedicines 2025, 13(8), 1837; https://doi.org/10.3390/biomedicines13081837 - 28 Jul 2025
Abstract
Following lung cancer, prostate cancer is the leading cause of cancer death in men. High-risk localized tumor burden or metastatic disease often progresses, refractory to initial treatment regimens. There is ongoing development of technology to appropriately identify high-risk patients, stage them correctly, and [...] Read more.
Following lung cancer, prostate cancer is the leading cause of cancer death in men. High-risk localized tumor burden or metastatic disease often progresses, refractory to initial treatment regimens. There is ongoing development of technology to appropriately identify high-risk patients, stage them correctly, and offer appropriate treatments to obtain the best clinical outcomes. Prostate cancer-specific membrane antigen (PSMA) is a transmembrane glutamate carboxypeptidase, which helps regulate folate absorption, and its overexpression is pathologically directly proportional and associated with prostate cancer. Increased PSMA expression is a known independent risk factor for poorer survival, and most metastatic lesions in CRPC are PSMA positive. Over the last decade, several PSMA-based PET radiopharmaceuticals have demonstrated superior sensitivities and specificities compared to traditional imaging methods. These outcomes have been demonstrated by several large clinical trials. As the data emerges, these diagnostics are being integrated into standard of care protocol to facilitate nuanced identification of malignant lesions. PSMA is also being targeted through several therapeutics, including radioligands and immunotherapies such as CAR-T, BiTEs, and ADCs. This review will discuss the landscape of PSMA-based theranostics in the context of prostate cancer. Full article
(This article belongs to the Special Issue Advanced Research on Genitourinary Cancer)
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37 pages, 3106 KiB  
Review
Quantum Dot-Enabled Biosensing for Prostate Cancer Diagnostics
by Hossein Omidian, Erma J. Gill and Luigi X. Cubeddu
Nanomaterials 2025, 15(15), 1162; https://doi.org/10.3390/nano15151162 - 28 Jul 2025
Abstract
Prostate cancer diagnostics are rapidly advancing through innovations in nanotechnology, biosensing strategies, and molecular recognition. This review analyzes studies focusing on quantum dot (QD)-based biosensors for detecting prostate cancer biomarkers with high sensitivity and specificity. It covers diverse sensing platforms and signal transduction [...] Read more.
Prostate cancer diagnostics are rapidly advancing through innovations in nanotechnology, biosensing strategies, and molecular recognition. This review analyzes studies focusing on quantum dot (QD)-based biosensors for detecting prostate cancer biomarkers with high sensitivity and specificity. It covers diverse sensing platforms and signal transduction mechanisms, emphasizing the influence of the QD composition, surface functionalization, and bio interface engineering on analytical performance. Key metrics such as detection limits, dynamic range, and compatibility with biological samples, including serum, urine, and tissue, are critically assessed. Recent advances in green-synthesized QDs and smartphone-integrated diagnostic platforms are highlighted, including lateral flow assays, paper-based devices, and pH-responsive hydrogels for real-time, low-cost, and decentralized cancer screening. These innovations enable multiplexed biomarker detection and tumor microenvironment monitoring in point-of-care settings. This review concludes by addressing the current limitations, scalability challenges, and future research directions for translating QD-enabled biosensors into clinically viable diagnostic tools. Full article
(This article belongs to the Section Nanofabrication and Nanomanufacturing)
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19 pages, 1282 KiB  
Article
The Role of Radiomic Analysis and Different Machine Learning Models in Prostate Cancer Diagnosis
by Eleni Bekou, Ioannis Seimenis, Athanasios Tsochatzis, Karafyllia Tziagkana, Nikolaos Kelekis, Savas Deftereos, Nikolaos Courcoutsakis, Michael I. Koukourakis and Efstratios Karavasilis
J. Imaging 2025, 11(8), 250; https://doi.org/10.3390/jimaging11080250 - 23 Jul 2025
Viewed by 218
Abstract
Prostate cancer (PCa) is the most common malignancy in men. Precise grading is crucial for the effective treatment approaches of PCa. Machine learning (ML) applied to biparametric Magnetic Resonance Imaging (bpMRI) radiomics holds promise for improving PCa diagnosis and prognosis. This study investigated [...] Read more.
Prostate cancer (PCa) is the most common malignancy in men. Precise grading is crucial for the effective treatment approaches of PCa. Machine learning (ML) applied to biparametric Magnetic Resonance Imaging (bpMRI) radiomics holds promise for improving PCa diagnosis and prognosis. This study investigated the efficiency of seven ML models to diagnose the different PCa grades, changing the input variables. Our studied sample comprised 214 men who underwent bpMRI in different imaging centers. Seven ML algorithms were compared using radiomic features extracted from T2-weighted (T2W) and diffusion-weighted (DWI) MRI, with and without the inclusion of Prostate-Specific Antigen (PSA) values. The performance of the models was evaluated using the receiver operating characteristic curve analysis. The models’ performance was strongly dependent on the input parameters. Radiomic features derived from T2WI and DWI, whether used independently or in combination, demonstrated limited clinical utility, with AUC values ranging from 0.703 to 0.807. However, incorporating the PSA index significantly improved the models’ efficiency, regardless of lesion location or degree of malignancy, resulting in AUC values ranging from 0.784 to 1.00. There is evidence that ML methods, in combination with radiomic analysis, can contribute to solving differential diagnostic problems of prostate cancers. Also, optimization of the analysis method is critical, according to the results of our study. Full article
(This article belongs to the Section Medical Imaging)
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31 pages, 2314 KiB  
Review
Innovative Peptide Therapeutics in the Pipeline: Transforming Cancer Detection and Treatment
by Yanyamba Nsereko, Amy Armstrong, Fleur Coburn and Othman Al Musaimi
Int. J. Mol. Sci. 2025, 26(14), 6815; https://doi.org/10.3390/ijms26146815 - 16 Jul 2025
Viewed by 519
Abstract
Cancer remains a leading global health burden, profoundly affecting patient survival and quality of life. Current treatments—including chemotherapy, radiotherapy, immunotherapy, and surgery—are often limited by toxicity or insufficient specificity. Conventional chemotherapy, for instance, indiscriminately attacks rapidly dividing cells, causing severe side effects. In [...] Read more.
Cancer remains a leading global health burden, profoundly affecting patient survival and quality of life. Current treatments—including chemotherapy, radiotherapy, immunotherapy, and surgery—are often limited by toxicity or insufficient specificity. Conventional chemotherapy, for instance, indiscriminately attacks rapidly dividing cells, causing severe side effects. In contrast, peptide-based therapeutics offer a paradigm shift, combining high tumour-targeting precision with minimal off-target effects. Their low immunogenicity, multi-pathway modulation capabilities, and adaptability for diagnostics and therapy make them ideal candidates for advancing oncology care. Innovative peptide platforms now enable three transformative applications: (1) precision molecular diagnostics (e.g., 18F-PSMA-1007 for prostate cancer detection), (2) targeted therapies (e.g., BT5528 and SAR408701 targeting tumour-specific antigens), and (3) theranostic systems (e.g., RAYZ-8009 and 177Lu-FAP-2286 integrating imaging and radiotherapy). Despite their promise, peptides face challenges like metabolic instability and short half-lives. Recent advances in structural engineering (e.g., cyclization and D-amino acid incorporation) and delivery systems (e.g., nanoparticles and PEGylation) have significantly enhanced their clinical potential. This review highlights peptide-based agents in development, showcasing their ability to improve early cancer detection, reduce metastasis, and enhance therapeutic efficacy with fewer adverse effects. Examples like CLP002 underscore their role in personalised medicine. By overcoming current limitations, peptide drugs are poised to redefine cancer management, offering safer, more effective alternatives to conventional therapies. Their integration into clinical practice could mark a critical milestone in achieving precision oncology. Full article
(This article belongs to the Special Issue Peptides as Biochemical Tools and Modulators of Biological Activity)
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16 pages, 769 KiB  
Article
[177Lu]Lu-PSMA-617 in Patients with Progressive PSMA+ mCRPC Treated With or Without Prior Taxane-Based Chemotherapy: A Phase 2, Open-Label, Single-Arm Trial in Japan
by Kouji Izumi, Ryuji Matsumoto, Yusuke Ito, Seiji Hoshi, Nobuaki Matsubara, Toshinari Yamasaki, Takashi Mizowaki, Atsushi Komaru, Satoshi Nomura, Toru Hattori, Hiroya Kambara, Shaheen Alanee, Makoto Hosono and Seigo Kinuya
Cancers 2025, 17(14), 2351; https://doi.org/10.3390/cancers17142351 - 15 Jul 2025
Viewed by 411
Abstract
Background: This Phase 2 trial evaluated the efficacy, tolerability, and safety of [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) in patients with ≥1 measurable lesion and progressive prostate-specific membrane antigen-positive (PSMA+) metastatic castration-resistant prostate cancer (mCRPC) in Japan. Methods: This study comprises four parts; [...] Read more.
Background: This Phase 2 trial evaluated the efficacy, tolerability, and safety of [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) in patients with ≥1 measurable lesion and progressive prostate-specific membrane antigen-positive (PSMA+) metastatic castration-resistant prostate cancer (mCRPC) in Japan. Methods: This study comprises four parts; data from three parts are presented here. Part 1 evaluated safety and tolerability; Parts 2 (post-taxane) and 3 (pre-taxane/taxane-naive) assessed the overall response rate (ORR; primary endpoint), overall survival (OS), radiographic progression-free survival (rPFS), disease control rate (DCR), PFS, and safety; and Part 4 is the expansion part. Patients received 7.4 GBq (±10%) 177Lu-PSMA-617 Q6W for up to six cycles. Results: Of the 35 patients who underwent a [68Ga]Ga-PSMA-11 (68Ga-PSMA-11) PET/CT scan, 30 received 177Lu-PSMA-617 (post-taxane, n = 12; pre-taxane, n = 18). No dose-limiting toxicity was noted in Part 1 (n = 3). Post- and pre-taxane patients had a median of three and five cycles, respectively. The primary endpoint, ORR, met the pre-specified threshold, with the lower limit of the 90% confidence interval (CI) above the threshold of 5% for post-taxane and 12% for pre-taxane. Post- and pre-taxane patients had an ORR of 25.0% (90% CI: 7.2–52.7) and 33.3% (90% CI: 15.6–55.4), respectively. In post- and pre-taxane patients, the DCR was 91.7% and 83.3%, the median rPFS was 3.71 and 12.25 months, and the median PFS was 3.71 and 5.59 months, respectively. The median OS was 14.42 and 12.94 months in post- and pre-taxane patients, respectively. The most common adverse events were constipation, decreased appetite, decreased platelet count, anemia, and nausea. Conclusions: The primary endpoint (ORR) was met. The safety profile of 177Lu-PSMA-617 was consistent with the VISION and PSMAfore studies, with no new safety signals in the Japanese patients with mCRPC. Full article
(This article belongs to the Section Cancer Therapy)
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23 pages, 625 KiB  
Review
Radionuclides Landscape in Prostate Cancer Theranostics
by Monica Neagu, Carolina Constantin, Mihail Eugen Hinescu, Petrisor Gabriel Bleotu, Mara-Georgiana Popovici, Maria-Iulia Zai and Klaus Michael Spohr
Int. J. Mol. Sci. 2025, 26(14), 6751; https://doi.org/10.3390/ijms26146751 - 14 Jul 2025
Viewed by 1083
Abstract
Prostate cancer, a malignancy of significant prevalence, affects approximately half a million men in Europe, with one in twelve males receiving a diagnosis before reaching the age of 75. Radiotheranostics represents a paradigm shift in prostate cancer treatment, leveraging radionuclides for diagnostic and [...] Read more.
Prostate cancer, a malignancy of significant prevalence, affects approximately half a million men in Europe, with one in twelve males receiving a diagnosis before reaching the age of 75. Radiotheranostics represents a paradigm shift in prostate cancer treatment, leveraging radionuclides for diagnostic and therapeutic applications, with PSMA emerging as the primary molecular target. Regulatory bodies have approved various PSMA-targeted radiodiagnostic agents, such as [18F]DCFPyL (PYLARIFY®, Lantheus Holdings), [18F]rhPSMA-7.3 (POSLUMA®, Blue Earth Diagnostics), and [68Ga]Ga-PSMA-11 (LOCAMETZ®, Novartis/ILLUCCIX®, Telix Pharmaceuticals), as well as therapeutic agents like [177Lu]Lu-PSMA-617 (PLUVICTO®, 15 Novartis). The approval of PLUVICTO® in March 2022 for patients with metastatic castration-resistant prostate cancer who have undergone prior treatments, including androgen receptor pathway-targeting agents and taxane-based chemotherapy, represents a significant advancement. Other radionuclides like 161Tb, 149Tb, 225Ac, 227Th, 223Ra, 211At, 213 Bi, 212Pb, 89Zr, and 125I are presented, emphasizing their clinical implementation or the stage of clinical trial they are in in the flow to biomedical implementation. Three clinically wise used radionuclides 177Lu, 225Ac, 223Ra are shown along with their characteristics. This review aims to elucidate the molecular mechanisms underpinning PSMA, explore the clinical applications of PSMA-targeted radiotheranostics, and critically examine the diverse challenges these therapies encounter in the treatment of prostate cancer. Full article
(This article belongs to the Section Molecular Oncology)
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13 pages, 887 KiB  
Article
Substantiation of Prostate Cancer Risk Calculator Based on Physical Activity, Lifestyle Habits, and Underlying Health Conditions: A Longitudinal Nationwide Cohort Study
by Jihwan Park
Appl. Sci. 2025, 15(14), 7845; https://doi.org/10.3390/app15147845 - 14 Jul 2025
Viewed by 166
Abstract
Purpose: Despite increasing rates of prostate cancer among men, prostate cancer risk assessments continue to rely on invasive laboratory tests like prostate-specific antigen and Gleason score tests. This study aimed to develop a noninvasive, data-driven risk model for patients to evaluate themselves [...] Read more.
Purpose: Despite increasing rates of prostate cancer among men, prostate cancer risk assessments continue to rely on invasive laboratory tests like prostate-specific antigen and Gleason score tests. This study aimed to develop a noninvasive, data-driven risk model for patients to evaluate themselves before deciding whether to visit a hospital. Materials and Methods: To train the model, data from the National Health Insurance Sharing Service cohort datasets, comprising 347,575 individuals, including 1928 with malignant neoplasms of the prostate, 5 with malignant neoplasms of the penis, 18 with malignant neoplasms of the testis, and 14 with malignant neoplasms of the epididymis, were used. The risk model harnessed easily accessible inputs, such as history of treatment for diseases including stroke, heart disease, and cancer; height; weight; exercise days per week; and duration of smoking. An additional 286,727 public datasets were obtained from the National Health Insurance Sharing Service, which included 434 (0.15%) prostate cancer incidences. Results: The risk calculator was built based on Cox proportional hazards regression, and I validated the model by calibration using predictions and observations. The concordance index was 0.573. Additional calibration of the risk calculator was performed to ensure confidence in accuracy verification. Ultimately, the actual proof showed a sensitivity of 60 (60.5) for identifying a high-risk population. Conclusions: The feasibility of the model to evaluate prostate cancer risk without invasive tests was demonstrated using a public dataset. As a tool for individuals to use before hospital visits, this model could improve public health and reduce social expenses for medical treatment. Full article
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17 pages, 1445 KiB  
Article
A Deep Learning Model Integrating Clinical and MRI Features Improves Risk Stratification and Reduces Unnecessary Biopsies in Men with Suspected Prostate Cancer
by Emiliano Bacchetti, Axel De Nardin, Gianluca Giannarini, Lorenzo Cereser, Chiara Zuiani, Alessandro Crestani, Rossano Girometti and Gian Luca Foresti
Cancers 2025, 17(13), 2257; https://doi.org/10.3390/cancers17132257 - 7 Jul 2025
Viewed by 376
Abstract
Background: Accurate upfront risk stratification in suspected clinically significant prostate cancer (csPCa) may reduce unnecessary prostate biopsies. Integrating clinical and Magnetic Resonance Imaging (MRI) variables using deep learning could improve prediction. Methods: We retrospectively analysed 538 men who underwent MRI and biopsy between [...] Read more.
Background: Accurate upfront risk stratification in suspected clinically significant prostate cancer (csPCa) may reduce unnecessary prostate biopsies. Integrating clinical and Magnetic Resonance Imaging (MRI) variables using deep learning could improve prediction. Methods: We retrospectively analysed 538 men who underwent MRI and biopsy between April 2019-September 2024. A fully connected neural network was trained using 5-fold cross-validation. Model 1 included clinical features (age, prostate-specific antigen [PSA], PSA density, digital rectal examination, family history, prior negative biopsy, and ongoing therapy). Model 2 used MRI-derived Prostate Imaging Reporting and Data System (PI-RADS) categories. Model 3 used all previous variables as well as lesion size, location, and prostate volume as determined on MRI. Results: Model 3 achieved the highest area under the receiver operating characteristic curve (AUC = 0.822), followed by Model 2 (AUC = 0.778) and Model 1 (AUC = 0.716). Sensitivities for detecting clinically significant prostate cancer (csPCa) were 87.4%, 91.6%, and 86.8% for Models 1, 2, and 3, respectively. Although Model 3 had slightly lower sensitivity than Model 2, it showed higher specificity, reducing false positives and avoiding 43.4% and 21.2% more biopsies compared to Models 1 and 2. Decision curve analysis showed M2 had the highest net benefit at risk thresholds ≤ 20%, while M3 was superior above 20%. Conclusions: Model 3 improved csPCa risk stratification, particularly in biopsy-averse settings, while Model 2 was more effective in cancer-averse scenarios. These models support personalized, context-sensitive biopsy decisions. Full article
(This article belongs to the Special Issue Radiomics in Cancer)
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25 pages, 4259 KiB  
Article
Towards Dual-Tracer SPECT for Prostate Cancer Imaging Using [99mTc]Tc-PSMA-I&S and [111In]In-RM2
by Carolina Giammei, Theresa Balber, Veronika Felber, Thomas Dillinger, Jens Cardinale, Marie R. Brandt, Anna Stingeder, Markus Mitterhauser, Gerda Egger and Thomas L. Mindt
Pharmaceuticals 2025, 18(7), 1002; https://doi.org/10.3390/ph18071002 - 3 Jul 2025
Viewed by 440
Abstract
Background/Objectives: Radiolabeled biomolecules specifically targeting overexpressed structures on tumor cells hold great potential for prostate cancer (PCa) imaging and therapy. Due to heterogeneous target expression, single radiopharmaceuticals may not detect or treat all lesions, while simultaneously applying two or more radiotracers potentially [...] Read more.
Background/Objectives: Radiolabeled biomolecules specifically targeting overexpressed structures on tumor cells hold great potential for prostate cancer (PCa) imaging and therapy. Due to heterogeneous target expression, single radiopharmaceuticals may not detect or treat all lesions, while simultaneously applying two or more radiotracers potentially improves staging, stratification, and therapy of cancer patients. This study explores a dual-tracer SPECT approach using [111In]In-RM2 (targeting the gastrin-releasing peptide receptor, GRPR) and [99mTc]Tc-PSMA-I&S (targeting the prostate-specific membrane antigen, PSMA) as a proof of concept. To mimic heterogeneous tumor lesions in the same individual, we aimed to establish a dual xenograft mouse model for preclinical evaluation. Methods: CHO-K1 cells underwent lentiviral transduction for human GRPR or human PSMA overexpression. Six-to-eight-week-old female immunodeficient mice (NOD SCID) were subsequently inoculated with transduced CHO-K1 cells in both flanks, enabling a dual xenograft with similar target density and growth of both xenografts. Respective dual-isotope imaging and γ-counting protocols were established. Target expression was analyzed ex vivo by Western blotting. Results: In vitro studies showed similar target-specific binding and internalization of [111In]In-RM2 and [99mTc]Tc-PSMA-I&S in transduced CHO-K1 cells compared to reference lines PC-3 and LNCaP. However, in vivo imaging showed negligible tumor uptake in xenografts of the transduced cell lines. Ex vivo analysis indicated a loss of the respective biomarkers in the xenografts. Conclusions: Although the technical feasibility of a dual-tracer SPECT imaging approach using 111In and 99mTc has been demonstrated, the potential of [99mTc]Tc-PSMA-I&S and [111In]In-RM2 in a dual-tracer cocktail to improve PCa diagnosis could not be verified. The animal model, and in particular the transduced cell lines developed exclusively for this project, proved to be unsuitable for this purpose. The in/ex vivo experiments indicated that results from an in vitro model may not necessarily be successfully transferred to an in vivo setting. To assess the potential of this dual-tracer concept to improve PCa diagnosis, optimized in vivo models are needed. Nevertheless, our strategies address key challenges in dual-tracer applications, aiming to optimize future SPECT imaging approaches. Full article
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14 pages, 3070 KiB  
Article
Immunosensor Enhanced with Silver Nanocrystals for On-Chip Prostate-Specific Antigen Detection
by Timothy A. Okhai, Kefilwe V. Mokwebo, Marlon Oranzie, Usisipho Feleni and Lukas W. Snyman
Biosensors 2025, 15(7), 428; https://doi.org/10.3390/bios15070428 - 3 Jul 2025
Viewed by 320
Abstract
An electrochemical immunosensor for the quantification of prostate-specific antigens (PSAs) using silver nanocrystals (AgNCs) is reported. The silver nanocrystals were synthesized using a conventional citrate reduction protocol. The silver nanocrystals were characterized using scanning electron microscopy (SEM) and field effect scanning electron microscopy [...] Read more.
An electrochemical immunosensor for the quantification of prostate-specific antigens (PSAs) using silver nanocrystals (AgNCs) is reported. The silver nanocrystals were synthesized using a conventional citrate reduction protocol. The silver nanocrystals were characterized using scanning electron microscopy (SEM) and field effect scanning electron microscopy (FESEM), X-ray diffraction (XRD), high-resolution transmission electron microscopy (HRTEM), Fourier-transform infrared spectroscopy (FTIR), UV-Vis spectroscopy, and small-angle X-ray scattering (SAXS). The proposed immunosensor was fabricated on a glassy carbon electrode (GCE), sequentially, by drop-coating AgNCs, the electro-deposition of EDC-NHS, the immobilization of anti-PSA antibody (Ab), and dropping of bovine serum albumin (BSA) to prevent non-specific binding sites. Each stage of the fabrication process was characterized by cyclic voltammetry (CV). Using square wave voltammetry (SWV), the proposed immunosensor displayed high sensitivity in detecting PSA over a concentration range of 1 to 10 ng/mL with a detection limit of 1.14 ng/mL and R2 of 0.99%. The immunosensor was selective in the presence of interfering substances like glucose, urea, L-cysteine, and alpha-methylacyl-CoA racemase (AMACR) and it showed good stability and repeatability. These results compare favourably with some previously reported results on similar or related technologies for PSA detection. Full article
(This article belongs to the Special Issue Photonics for Bioapplications: Sensors and Technology—2nd Edition)
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17 pages, 2255 KiB  
Article
Engineering a Radiohybrid PSMA Ligand with an Albumin-Binding Moiety and Pharmacokinetic Modulation via an Albumin-Binding Competitor for Radiotheranostics
by Saki Hirata, Hiroaki Echigo, Masayuki Munekane, Kenji Mishiro, Kohshin Washiyama, Takeshi Fuchigami, Hiroshi Wakabayashi, Kazuhiro Takahashi, Seigo Kinuya and Kazuma Ogawa
Molecules 2025, 30(13), 2804; https://doi.org/10.3390/molecules30132804 - 29 Jun 2025
Viewed by 380
Abstract
The prostate-specific membrane antigen (PSMA) is a well-established target for radiotheranostics in prostate cancer. We previously demonstrated that 4-(p-astatophenyl)butyric acid (APBA), an albumin-binding moiety (ABM) labeled with astatine-211 (211At), enables the modulation of pharmacokinetics and enhancement of therapeutic efficacy [...] Read more.
The prostate-specific membrane antigen (PSMA) is a well-established target for radiotheranostics in prostate cancer. We previously demonstrated that 4-(p-astatophenyl)butyric acid (APBA), an albumin-binding moiety (ABM) labeled with astatine-211 (211At), enables the modulation of pharmacokinetics and enhancement of therapeutic efficacy when combined with the post-administration of an albumin-binding competitor. However, this strategy has not been explored in PSMA-targeting ligands. We designed and synthesized [211At]6, a novel PSMA ligand structurally analogous to PSMA-617 with APBA. The compound was obtained via a tin–halogen exchange reaction from the corresponding tributylstannyl precursor. Comparative cellular uptake and biodistribution studies were conducted with [211At]6, its radioiodinated analog [125I]5, and [67Ga]Ga-PSMA-617. To assess pharmacokinetic modulation, sodium 4-(p-iodophenyl)butanoate (IPBA), an albumin-binding competitor, was administered 1 h postinjection of [125I]5 and [211At]6 at a 10-fold molar excess relative to blood albumin. The synthesis of [211At]6 gave a radiochemical yield of 15.9 ± 7.7% and a radiochemical purity > 97%. The synthesized [211At]6 exhibited time-dependent cellular uptake and internalization, with higher uptake levels than [67Ga]Ga-PSMA-617. Biodistribution studies of [211At]6 in normal mice revealed a prolonged blood retention similar to those of [125I]5. Notably, post-administration of IPBA significantly reduced blood radioactivity and non-target tissue accumulation of [125I]5 and [211At]6. We found that ABM-mediated pharmacokinetic control was applicable to PSMA-targeted radiotherapeutics, broadening its potential for the optimization of radiotheranostics. Full article
(This article belongs to the Special Issue Advance in Radiochemistry, 2nd Edition)
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19 pages, 588 KiB  
Review
Targeting Glypican-3 in Liver Cancer: Groundbreaking Preclinical and Clinical Insights
by Luca Filippi, Viviana Frantellizzi, Luca Urso, Giuseppe De Vincentis and Nicoletta Urbano
Biomedicines 2025, 13(7), 1570; https://doi.org/10.3390/biomedicines13071570 - 26 Jun 2025
Viewed by 735
Abstract
Positron emission tomography (PET) imaging targeting glypican-3 (GPC3) holds promise for improving the detection and characterization of hepatocellular carcinoma (HCC). Preclinical and early clinical studies have largely utilized high-molecular-weight antibodies radiolabeled with isotopes such as 89Zr and 124I, demonstrating high affinity [...] Read more.
Positron emission tomography (PET) imaging targeting glypican-3 (GPC3) holds promise for improving the detection and characterization of hepatocellular carcinoma (HCC). Preclinical and early clinical studies have largely utilized high-molecular-weight antibodies radiolabeled with isotopes such as 89Zr and 124I, demonstrating high affinity and tumor uptake but suffering from prolonged circulation times and suboptimal signal-to-background ratios. To address these limitations, interest has shifted toward low-molecular-weight vectors—synthetic peptides and small antibody fragments—labeled with shorter-lived radionuclides (e.g., 68Ga and 18F) to enable rapid pharmacokinetics and same-day imaging protocols. Emerging platforms such as affibodies and aptamers offer further advantages in target affinity and reduced immunogenicity. However, clinical translation requires rigorous validation: larger, histologically confirmed cohorts, head-to-head comparison with CT/MRI, and correlation with hard clinical endpoints. Moreover, leveraging GPC3 expression as a biomarker could guarantee a deeper knowledge of tumor biology—differentiation grade and vascular invasion risk—and guide theranostic strategies. While β-emitters (90Y, 177Lu) have been explored for GPC3-directed therapy, their efficacy is influenced by oxygenation and cell-cycle status, whereas α-emitters (225Ac) may overcome these constraints, albeit with challenges in radionuclide selection and daughter nuclide management. Finally, dual-targeting probes combining GPC3 and prostate-specific membrane antigen (PSMA) have demonstrated superior uptake and retention in murine models, suggesting a versatile approach for future clinical diagnostics and therapy planning. Full article
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28 pages, 7186 KiB  
Review
Advances and Challenges in Prostate Cancer Diagnosis: A Comprehensive Review
by Emil Kania, Maciej Janica, Miłosz Nesterowicz, Wojciech Modzelewski, Mateusz Cybulski and Jacek Janica
Cancers 2025, 17(13), 2137; https://doi.org/10.3390/cancers17132137 - 25 Jun 2025
Viewed by 818
Abstract
Prostate cancer is the most commonly diagnosed malignancy in men and continues to be a leading cause of cancer-related mortality. Accurate and timely diagnosis is essential for distinguishing clinically significant tumors from indolent lesions and for informing treatment decisions. Multiparametric magnetic resonance imaging [...] Read more.
Prostate cancer is the most commonly diagnosed malignancy in men and continues to be a leading cause of cancer-related mortality. Accurate and timely diagnosis is essential for distinguishing clinically significant tumors from indolent lesions and for informing treatment decisions. Multiparametric magnetic resonance imaging (mpMRI) has revolutionized prostate cancer detection by enabling precise lesion localization, risk stratification, and improved biopsy targeting. Fusion biopsy, which combines mpMRI findings with real-time transrectal ultrasonography (TRUS), has emerged as a highly effective method for sampling suspicious lesions. This review provides an integrated anatomical, epidemiological, technical, and clinical overview that highlights the evolving role of fusion biopsy in contemporary prostate cancer diagnostics. We also explore emerging strategies such as penumbra-targeted sampling, discuss ongoing clinical challenges, and examine the impact of biopsy underestimation and lack of standardization. Compared to conventional systematic biopsy, mpMRI-TRUS fusion biopsy improves the detection of clinically significant prostate cancer while reducing the overdiagnosis of low-risk tumors. To our knowledge, few recent reviews have comprehensively synthesized current clinical guidelines, emerging biopsy techniques, and future directions within a single narrative. mpMRI-TRUS-guided fusion biopsy represents a major advancement in the prostate cancer diagnostic pathway, promoting precision oncology by reducing overtreatment and facilitating individualized patient care. This review aims to assist clinicians in adopting biopsy innovations that enhance diagnostic accuracy and improve patient outcomes. Full article
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11 pages, 399 KiB  
Article
Multiple or More Severe Grade Prevalent Vertebral Fractures Are Associated with Higher All-Cause Mortality in Men with Nonmetastatic Prostate Cancer Receiving Androgen Deprivation Therapy
by Kashia Goto, Daisuke Watanabe, Hiromitsu Takano, Kazuki Yanagida, Norikazu Kawae, Hajime Kajihara and Akio Mizushima
Cancers 2025, 17(13), 2131; https://doi.org/10.3390/cancers17132131 - 25 Jun 2025
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Abstract
Background/Objectives: Prognostic information for nonmetastatic prostate cancer (nmPC) patients with prevalent vertebral fractures (PVFs) is very limited. Vertebral fractures can impair physical function, limit activities of daily living, and decrease quality of life. Prevention of vertebral fractures may be important to improve [...] Read more.
Background/Objectives: Prognostic information for nonmetastatic prostate cancer (nmPC) patients with prevalent vertebral fractures (PVFs) is very limited. Vertebral fractures can impair physical function, limit activities of daily living, and decrease quality of life. Prevention of vertebral fractures may be important to improve patient prognosis. This study aims to investigate the impact of the presence and severity of PVFs on overall survival in patients with nmPC undergoing androgen deprivation therapy (ADT). Methods: A total of 275 men (median age: 73 years) with nmPC who underwent ADT were studied retrospectively. The median observation period was 55 months. Variables included age, body mass index, T classification, N classification, Gleason score, and pretreatment serum prostate-specific antigen levels. PVF was diagnosed from the sagittal computed tomography images of Th1 to L5 before initiating ADT, and the severity was determined by the number of PVFs and the Semiquantitative (SQ) method. Hazard ratios and 95% confidence intervals for overall survival were calculated using the Cox proportional hazards model. Results: During the observation period, 30 patients died from all causes. Multivariate Cox regression analysis identified multiple PVFs and high-grade PVFs, as determined by the SQ method, as significant predictors of overall survival. The analysis utilized two adjustment models: one adjusted for age only and the other adjusted for age, Gleason score, and clinical T stage. Conclusions: Multiple PVFs and high-grade PVF determined by the SQ method prior to ADT initiation were associated with higher all-cause mortality in nmPC patients treated with ADT. Full article
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