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Imaging of Prostate-Specific Membrane Antigen with Small-Molecule PET Radiotracers: From the Bench to Advanced Clinical Applications
摘要： In recent years, small-molecule inhibitors of prostate-specific membrane antigen (PSMA) labeled with radionuclides that allow for positron emission tomography (PET) imaging have been extensively studied in many clinical contexts in men with prostate cancer (PCa). The high sensitivity and specificity of these agents for identifying sites of PCa has quickly led to their widespread adoption as a de facto clinical standard of care throughout much of the world. PSMA-targeted PET radiotracers have been particularly well-studied in preoperatively staging men with high-risk PCa, evaluating biochemical recurrence following definitive therapy, and guiding metastasis-directed therapy in patients suspected of having oligorecurrent/oligometastatic disease. Furthermore, the expression of PSMA on the tumor neovasculature of many nonprostate malignancies has enabled a burgeoning subfield concentrated on delineating the potential utility of PSMA-targeted PET agents for imaging other cancers. In this review, we highlight the preclinical development of key small molecules that are now being clinically utilized for PCa imaging, discuss the roles of PSMA-targeted agents in guiding patient management, and consider the role these compounds may play in imaging nonprostate cancers.
关键词： NAALADase,renal cell carcinoma,prostate cancer,glutamate carboxypeptidase II,tumor neovasculature
更新于2025-09-19 17:15:36
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Preclinical evaluation of a 64Cu-labeled disintegrin for PET imaging of prostate cancer
摘要： A novel recombinant disintegrin, vicrostatin (VCN), displays high binding affinity to a broad range of human integrins in substantial competitive biological advantage over other integrin-based antagonists. In this study, we synthesized a new 64Cu-labeled VCN probe and evaluated its imaging properties for prostate cancer in PC-3 tumor-bearing mice. Macrocyclic chelating agent 1,8-diamino-3,6,10,13,16,19-hexaazabicyclo[6.6.6]-eicosine (DiAmSar) was conjugated with PEG unit and followed by coupling with VCN. The precursor was then radiolabeled with positron emitter 64Cu (t1/2 = 12.7 h) in ammonium acetate buffer to provide 64Cu-Sar-PEG-VCN, which was subsequently subjected to in vitro studies, small animal PET, and biodistribution studies. The PC-3 tumor-targeting efficacy of 64Cu-Sar-PEG-VCN was compared to a cyclic RGD peptide-based PET probe (64Cu-Sar-RGD). 64Cu labeling was achieved in 75% decay-corrected yield with radiochemical purity of > 98%. The specific activity of 64Cu-Sar-PEG-VCN was estimated to be 37 MBq/nmol. MicroPET imaging results showed that 64Cu-Sar-PEG-VCN has preferential tumor uptake and good tumor retention in PC-3 tumor xenografts. As compared to 64Cu-Sar-RGD, 64Cu-Sar-PEG-VCN produces higher tumor-to-muscle (T/M) imaging contrast ratios at 2 h (4.66 ± 0.34 vs. 2.88 ± 0.46) and 24 h (4.98 ± 0.80 vs. 3.22 ± 0.30) post-injection (pi) and similar tumor-to-liver ratios at 2 h (0.43 ± 0.09 vs. 0.37 ± 0.04) and 24 h (0.57 ± 0.13 vs. 0.52 ± 0.07) pi. The biodistribution results were consistent with the quantitative analysis of microPET imaging, demonstrating good T/M ratio (2.73 ± 0.36) of 64Cu-Sar-PEG-VCN at 48 h pi in PC-3 tumor xenografts. For both microPET and biodistribution studies at 48 h pi, the PC-3 tumor uptake of 64Cu-Sar-PEG-VCN is lower than that of 64Cu-Sar-RGD. 64Cu-Sar-PEG-VCN has the potential for in vivo imaging of prostate cancer with PET, which may provide a unique non-invasive method to quantitatively localize and characterize prostate cancer.
关键词： Angiogenesis,Disintegrin,PET imaging,Prostate cancer,64Cu,Vicrostatin
更新于2025-09-19 17:13:59
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Dual-color magnetic-quantum dot nanobeads as versatile fluorescent probes in test strip for simultaneous point-of-care detection of free and complexed prostate-specific antigen
摘要： Simultaneous detection of free and complexed prostate-specific antigen (f-PSA and c-PSA) is critical to the prostate cancer (PCa) diagnostic accuracy for clinical samples with PSA values in the diagnostic gray zone between 4 and 10 ng mL?1. Herein, red and green magnetic-quantum dot nanobeads (MQBs) with superior magnetic property and high luminescence were fabricated via polyethyleneimine-mediated electrostatic adsorption of numerous quantum dots onto superparamagnetic Fe3O4 magnetic cores, and were conjugated with f-PSA antibody and c-PSA antibody, respectively, as versatile fluorescent probes in test strip for immune recognition, magnetic enrichment, and simultaneous detection of f-PSA and c-PSA analytes in complex biological matrix with t-PSA antibody on the test line. A low-cost and portable smartphone readout device with an application was also developed for the imaging of dual-color test strips and data processing. This assay can simultaneously detect f-PSA and c-PSA with the limits of detection of 0.009 ng mL?1 and 0.087 ng mL?1, respectively. Clinical serum samples of PCa and benign prostatic hyperplasia patients were evaluated to confirm the clinical feasibility. The results suggest that the proposed dual-color MQBs-based fluorescent lateral flow immunoassay is a promising point-of-care diagnostics technique for the accurate diagnosis of PCa even in resource-limited settings.
关键词： Free and complexed prostate-specific antigen,Fluorescent lateral flow immunoassay,Simultaneous detection,Prostate cancer,Magnetic-quantum dot nanobead,Point-of-care
更新于2025-09-16 10:30:52
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Determination of prostate cancer marker Zn2+ with a highly selective surface-enhanced Raman scattering probe on liquid–liquid self-assembled Au nanoarrays
摘要： As the concentration of Zn2+ in patients with prostate cancer is much less than that in healthy persons, Zn2+ concentration can be used as a marker to expediently screen prostate cancer. In this study, a sensitive and highly selective surface-enhanced Raman scattering (SERS) method to detect Zn2+ concentration in human prostatic fluids by utilizing water-insoluble 2-carboxyl-2′-hydroxyl-5′-sulfoformazylbenze (Zincon) as a SERS probe based on self-assembled Au nanoarrays at a liquid–liquid interface between n-hexane and Au colloids was proposed. Zincon showed remarkably different SERS bands before and after coordinating Zn2+ in the controlled conditions (70 μL of ethanol, 500 μL of n-hexane, pH value of 7.1 and 10 s of vortex mixing time), which can be used in quantifying Zn2+ with characteristic peaks. The proposed SERS method presented a good linear relationship ranging from 0.5 to 10 μmol/L and a satisfactory detection limit of 0.1 μmol/L as well as low interference with other metal ions. Moreover, the detection results are close to those of the conventional standard atomic absorption spectroscopy (AAS) method.
关键词： SERS,Au nanoarray,Zincon,Zn2+,Liquid-liquid self-assembly,Prostate cancer
更新于2025-09-12 10:27:22
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Magnetic resonance image‐guided focal laser ablation in clinically localized prostate cancer: safety and efficacy
摘要： Background: To evaluate the safety and efficacy of focal laser ablation (FLA) in low-intermediate risk prostate cancer. Methods: Inclusion criteria were men aged 50–75 years, prostate-specific antigen (PSA) ≤15 ng/mL, clinical stage T1c–T2a, one or two lesions (PI-RADS ≥3) on magnetic resonance imaging (MRI), and Gleason score 6 (>3 mm) or Gleason 7 on targeted biopsy. Treatment success was defined as no clinically significant cancer in ablated areas. The study is prospective. Under MRI guidance, laser ablation was applied to the visible lesion(s). International Prostate Symptoms Score, Sexual Health Inventory in Men score and PSA levels were assessed at baseline and repeated at 1, 3, 6, 12 and 18 months. MRI was repeated at 3 and 12 months. Cancer control was assessed at 6 months using targeted and systematic biopsies. Results: FLA was performed in 49 patients. Gleason scores were 3 + 3 in 13 patients (26.5%), 3 + 4 in 29 (59.2%) and 4 + 3 in 7 (14.3%). No significant complications were noticed. International Prostate Symptoms Score measurements up to 18 months were not different from baseline (all P > 0.05). Sexual Health Inventory in Men scores dropped in the first year (all P < 0.05), but were not different from baseline levels at 18 months (P = 0.097). PSA levels dropped significantly at 3–18 months (all P < 0.05). Treatment was successful in 39 patients (79.6%). Persistent cancer in treated areas was found in 10 patients (20.4%). Conclusions: FLA is safe with no impact on urinary and sexual functions at 18 months follow-up. Oncologic control is encouraging. Larger scale studies and longer follow-up are required.
关键词： Prostate cancer,Prostate cancer treatment outcome,Focal laser ablation,Focal therapy
更新于2025-09-11 14:15:04
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Comparing the Staging/Restaging Performance of 68Ga-Labeled Prostate-Specific Membrane Antigen and 18F-Choline PET/CT in Prostate Cancer
摘要： PET/CT using prostate-specific membrane antigen (PSMA) and choline radiotracers is widely used for diagnosis of prostate cancer. However, the roles of and differences in diagnostic performance between these 2 radiotracers for prostate cancer are unclear. The aim of this study was to compare the staging and restaging performance of 68Ga-labeled PSMA and 18F-choline PET/CT imaging in prostate cancer. Methods: A comprehensive search was performed in PubMed for studies reporting the staging performance of 68Ga-PSMA and 18F-choline PET/CT in prostate cancer from the inception of the database to October 1, 2018, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Thirty-five studies were included in this systematic review and meta-analysis. Pooled estimates of patient- and lesion-based sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) for 68Ga-PSMA and 18F-choline PET/CT were calculated alongside 95% confidence intervals. Summary receiver operating characteristic curves were plotted, and the area under the summary receiver operating characteristic curve (AUC) was determined alongside the Q* index. Results: The patient-based overall pooled sensitivity, specificity, PLR, NLR, DOR, and AUC of 68Ga-PSMA PET/CT for staging in prostate cancer (13 studies) were 0.92, 0.94, 7.91, 0.14, 79.04, and 0.96, respectively, whereas those of 18F-choline PET/CT (16 studies) were 0.93, 0.83, 4.98, 0.10, 68.27, and 0.95. The lesion-based overall pooled sensitivity, specificity, PLR, NLR, DOR, and AUC of 68Ga-PSMA PET/CT for staging in prostate cancer (9 studies) were 0.83, 0.95, 23.30, 0.17, 153.58, and 0.94, respectively, and those of 18F-choline PET/CT (4 studies) were 0.81, 0.92, 8.59, 0.20, 44.82, and 0.98. In both patient- and lesion-based imaging, there was no statistically significant difference in the abilities of detecting or excluding prostate cancer between 68Ga-PSMA PET/CT and 18F-choline PET/CT. Conclusions: For staging and restaging performance in patients with prostate cancer, there was no significant difference between 68Ga-PSMA PET/CT and 18F-choline PET/CT. 68Ga-PSMA PET/CT and 18F-choline PET/CT have demonstrated high diagnostic performance for accurate staging and restaging in patients with prostate cancer, and thus both should be considered for staging in this disease.
关键词： 18F-fluorocholine (18F-choline),PET,staging,prostate cancer,68Ga-PSMA CT
更新于2025-09-11 14:15:04
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Simultaneous 18F-fluciclovine Positron Emission Tomography and Magnetic Resonance Spectroscopic Imaging of Prostate Cancer
摘要： Purpose: To investigate the associations of metabolite levels derived from magnetic resonance spectroscopic imaging (MRSI) and 18F-?uciclovine positron emission tomography (PET) with prostate tissue characteristics. In a cohort of 19 high-risk prostate cancer patients that underwent simultaneous PET/MRI, we evaluated the diagnostic performance of MRSI and PET for discrimination of aggressive cancer lesions from healthy tissue and benign lesions. Data analysis comprised calculations of correlations of mean standardized uptake values (SUVmean), maximum SUV (SUVmax), and the MRSI-derived ratio of (total choline + spermine + creatine) to citrate (CSC/C). Whole-mount histopathology was used as gold standard. Results: The results showed a moderate signi?cant correlation between both SUVmean and SUVmax with CSC/C ratio. Conclusions: We demonstrated that the simultaneous acquisition of 18F-?uciclovine PET and MRSI with an integrated PET/MRI system is feasible and a combination of these imaging modalities has potential to improve the diagnostic sensitivity and speci?city of prostate cancer lesions.
关键词： citrate,benign prostatic hyperplasia,chemical shift imaging,prostate cancer,positron emission tomography,magnetic resonance spectroscopy
更新于2025-09-11 14:15:04
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Integration of PSMA-targeted PET imaging into the armamentarium for detecting clinically significant prostate cancer
摘要： To explore the current state of using prostate-specific membrane antigen (PSMA)-targeted PET imaging to aid in the diagnosis of clinically significant prostate cancer. Prostate-specific antigen screening remains controversial, as it is associated with the underdetection of clinically significant prostate cancer as well as the overdetection and subsequent overtreatment of clinically insignificant disease. A diagnostic test that can accurately assess the presence of clinically significant prostate cancer and avoid detection of low-risk tumors is needed. Multiparametric magnetic resonance imaging (mpMRI) can aid in the detection of clinically significant prostate cancer and can be used with fusion-based biopsy platforms to target biopsies to specific lesions. However, there are several limitations of mpMRI including a modest negative predictive value for high-grade cancer. PSMA-targeted PET imaging has shown promise as a noninvasive test to aid in the detection of clinically significant prostate cancer while providing anatomical information to guide targeted biopsies. PSMA-targeted PET in combination with mpMRI offers a higher degree of diagnostic accuracy for imaging localized prostate cancer than either modality alone. PSMA-targeted PET imaging can aid in the identification of men with clinically significant prostate cancer. Further research is needed to determine the full potential of PSMA-targeted imaging in both the detection and treatment of localized prostate cancer.
关键词： focal therapy,MRI/ultrasound fusion,prostate-specific membrane antigen,prostate cancer,targeted biopsy
更新于2025-09-10 09:29:36
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[IEEE 2018 24th International Conference on Pattern Recognition (ICPR) - Beijing, China (2018.8.20-2018.8.24)] 2018 24th International Conference on Pattern Recognition (ICPR) - A Novel ADCs-Based CNN Classification System for Precise Diagnosis of Prostate Cancer
摘要： This paper addresses the issue of early diagnosis of prostate cancer from diffusion-weighted magnetic resonance imaging (DWI) using a convolutional neural network (CNN) based computer-aided diagnosis (CAD) system. The proposed CNN-based CAD system first segments the prostate using a geometric deformable model. The evolution of this model is guided by a stochastic speed function that exploits first-and second-order appearance models besides shape prior. The fusion of these guiding criteria is accomplished using a nonnegative matrix factorization (NMF) model. Then, the apparent diffusion coefficients (ADCs) within the segmented prostate are calculated at each b-value. They are used as imaging markers for the blood diffusion of the scanned prostate. For the purpose of classification/diagnosis, a three dimensional CNN has been trained to extract the most discriminatory features of these ADC maps for distinguishing malignant from benign prostate tumors. The performance of the proposed CNN-based CAD system is evaluated using DWI datasets acquired from 45 patients (20 benign and 25 malignant) at seven different b-values. The acquisition of these DWI datasets is performed using two different scanners with different magnetic field strengths (1.5 Tesla and 3 Tesla). The conducted experiments on in-vivo data confirm that the use of ADCs makes the proposed system nonsensitive to the magnetic field strength.
关键词： Prostate Cancer,Convolutional Neural Networks,Apparent Diffusion Coefficients
更新于2025-09-10 09:29:36
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A Sample-to-Targeted Gene Analysis Biochip for Nanofluidic Manipulation of Solid-Phase Circulating Tumor Nucleic Acid Amplification in Liquid Biopsies
摘要： The use of circulating tumor nucleic acids (ctNA) in patient liquid biopsies for targeted genetic analysis is rapidly increasing in clinical oncology. Still, the call for an integrated methodology that is both rapid and sensitive for analyzing trace ctNA amount in liquid biopsies, has unfortunately not been fully realized. Herein, we performed complex liquid biopsy sample-to-targeted genetic analysis on a biochip with 50 copies-detection limit within 30 min. Our biochip uniquely integrated: 1) electrical lysis and release of cellular targets with minimal processing; 2) nanofluidic manipulation to accelerate molecular kinetics of solid-phase isothermal amplification; 3) single-step capture and amplification of multiple NA targets prior to nanozyme-mediated electrochemical detection. Using prostate cancer liquid biopsies, we successfully demonstrated multifunctionality for cancer risk prediction; correlation of serum and urine analyses; and cancer relapse monitoring.
关键词： solid-phase amplification,microfluidics,risk stratification,liquid biopsy,prostate cancer
更新于2025-09-10 09:29:36