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Initial evaluation of <scp>PET</scp> / <scp>CT</scp> with <sup>18</sup> F‐ <scp>FSU</scp> ‐880 targeting prostate‐specific membrane antigen in prostate cancer patients
摘要: This first-in-man study was carried out to evaluate the safety, whole-body distribution, dose estimation, and lesion accumulation of 18F-FSU-880, a newly developed probe targeting prostate-specific membrane antigen. Six prostate cancer patients with known metastatic lesions underwent serial whole-body PET/computed tomography (CT) with 18F-FSU-880. Blood and urine were analyzed before and after PET/CT. Accumulation of 18F-FSU-880 in organs and metastatic lesions in serial PET images were evaluated by measuring the standardized uptake values. From the biodistribution data, the organ doses and whole-body effective dose were calculated using OLINDA/EXM software. 18F-FSU-880 PET/CT could be carried out without significant adverse effects. High physiological uptake was observed in the salivary/lachrymal glands and kidneys. The effective dose was calculated to be 0.921 × 10?2 mSv/MBq. Known metastatic lesions were clearly visualized with high image contrast that increased with time, except in 1 patient, whose bone metastases were well-controlled and inactive. The PET/CT with 18F-FSU-880 could be carried out safely and could clearly visualize active metastatic lesions. The present results warrant further clinical studies with a larger number of cases to verify the clinical utility of 18F-FSU-880 PET/CT in the management of prostate cancer patients.
关键词: dosimetry,prostate cancer,prostate-specific membrane antigen,positron emission tomography/computed tomography,fluorine-18
更新于2025-09-23 15:23:52
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Eficacia de la imagen precoz con 68Ga-PSMA-I&T para la discriminación de lesiones en los pacientes con cáncer de próstata
摘要: Objective: 68Ga-PSMA-uptake shows accumulation in the malignant lesions of prostate cancer patients as early as 5 min p.i. Studies indicate the value of adding an early image of the pelvis to the imaging protocol of 68Ga-PSMA-11 PET/CT scan showed contradictory results. In this study we planned to assess the significance of an additional early imaging in 68Ga-PSMA-I&T PET/CT imaging in prostate cancer patients. Materials and methods: A total of 35 prostate cancer patients referred to 68Ga-PSMA-I&T PET/CT imaging for restaging of the disease due to suspicion of relapse after definitive therapy were enrolled. First an early static pelvic image was obtained at a maximum of 300 s following injection of the radiotracer. Sixty minutes postinjection a whole-body PET/CT scan was conducted with an emission time of 3 min per bed position. The lesions which were categorized as local recurrence, bone lesion and lymph node metastasis in the early images, were compared with the late images in terms of number of lesions detected and SUVmax values. Results: 68Ga-PSMA-I&T PET/CT was positive in 23 of 35 patients (65.7%). A pathological uptake was observed in the prostatic bed site, in the pelvic lymph nodes, and in the bones in 17 patients (48.5%), 12 patients (34.2%), and 13 patients (37.1%), respectively. In one patient, focal pathological increased uptake in the prostatic bed with a SUVmax value of 5.8 was detected but this lesion disappeared in the late images. The average SUVmax values of the lesions in the prostatic bed were 13.7 ± 12.1 versus 26.3 ± 23.8 in the 5 min and 60 min studies respectively (p < 0.001). In one patient, the pathological uptake in the lymph node in the early study cleared in the late study, whereas in another accumulation of activity was detected in a pelvic lymph node in the late study, while there was no lymph node detected in the early study. The average SUVmax values of the lymph nodes were 12.1 ± 8.8 versus 26.3 ± 22.6 in the 5 min and 60 min studies respectively (p < 0.001). The average SUVmax values of the bone lesions were 11.4 ± 6.9 versus 15 ± 10.7 in the 5 min and 60 min studies respectively. Conclusion: Our study is the first in the literature to evaluate the impact of adding an early static pelvic image to the 68Ga-PSMA-I&T scan, in the detection rate of the lesions. Although there was no marked discordance between the 2 sets of images, the addition of an early image to the imaging protocol of 68Ga-PSMA-I&T scan would increase the efficacy of detection of malignant lesions in the pelvis, which might show rapid clearance and has the risk of being masked by the urinary system activity.
关键词: Prostate-specific membrane antigen,68Ga-PSMA-I&T,PET/CT,Lymph node metastases,Prostate cancer
更新于2025-09-23 15:22:29
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Randomized prospective phase III trial of 68Ga-PSMA-11 PET/CT molecular imaging for prostate cancer salvage radiotherapy planning [PSMA-SRT]
摘要: Background: Salvage radiotherapy (SRT) for prostate cancer (PCa) recurrence after prostatectomy offers long-term biochemical control in about 50–60% of patients. SRT is commonly initiated in patients with serum PSA levels < 1 ng/mL, a threshold at which standard-of-care imaging is insensitive for detecting recurrence. As such, SRT target volumes are usually drawn in the absence of radiographically visible disease. 68Ga-PSMA-11 (PSMA) PET/CT molecular imaging is highly sensitive and may offer anatomic localization of PCa biochemical recurrence. However, it is unclear if incorporation of PSMA PET/CT imaging into the planning of SRT could improve its likelihood of success. The purpose of this trial is to evaluate the success rate of SRT for recurrence of PCa after prostatectomy with and without planning based on PSMA PET/CT. Methods: We will randomize 193 patients to proceed with standard SRT (control arm 1, n = 90) or undergo a PSMA PET/CT scan (free of charge for patients) prior to SRT planning (investigational arm 2, n = 103). The primary endpoint is the success rate of SRT measured as biochemical progression-free survival (BPFS) after initiation of SRT. Biochemical progression is defined by PSA ≥ 0.2 ng/mL and rising. The randomization ratio of 1:1.13 is based on the assumption that approximately 13% of subjects randomized to Arm 2 will not be treated with SRT because of PSMA-positive extra-pelvic metastases. These patients will not be included in the primary endpoint analysis but will still be followed. The choice of treating the prostate bed alone vs prostate bed and pelvic lymph nodes, with or without androgen deprivation therapy (ADT), is selected by the treating radiation oncologist. The radiation oncologist may change the radiation plan depending on the findings of the PSMA PET/CT scan. Any other imaging is allowed for SRT planning in both arms if done per routine care. Patients will be followed until either one of the following conditions occur: 5 years after the date of initiation of randomization, biochemical progression, diagnosis of metastatic disease, initiation of any additional salvage therapy, death. Discussion: This is the first randomized phase 3 prospective trial designed to determine whether PSMA PET/CT molecular imaging can improve outcomes in patients with PCa early BCR following radical prostatectomy. Acronym: PSMA-SRT Phase 3 trial.
关键词: Randomized phase 3 trial,PET/CT,Prostate cancer,PSMA,Salvage radiation therapy
更新于2025-09-23 15:22:29
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Dual-Modality ImmunoPET/Fluorescence Imaging of Prostate Cancer with an Anti-PSCA Cys-Minibody
摘要: Inadequate diagnostic methods for prostate cancer lead to over- and undertreatment, and the inability to intraoperatively visualize positive margins may limit the success of surgical resection. Prostate cancer visualization could be improved by combining the complementary modalities of immuno-positron emission tomography (immunoPET) for preoperative disease detection, and fluorescence imaging-guided surgery (FIGS) for real-time intraoperative tumor margin identification. Here, we report on the evaluation of dual-labeled humanized anti-prostate stem cell antigen (PSCA) cys-minibody (A11 cMb) for immunoPET/fluorescence imaging in subcutaneous and orthotopic prostate cancer models. Methods: A11 cMb was site-specifically conjugated with the near-infrared fluorophore Cy5.5 and radiolabeled with 124I or 89Zr. 124I-A11 cMb-Cy5.5 was used for successive immunoPET/fluorescence imaging of prostate cancer xenografts expressing high or moderate levels of PSCA (22Rv1-PSCA and PC3-PSCA). 89Zr-A11 cMb-Cy5.5 dual-modality imaging was evaluated in an orthotopic model. Ex vivo biodistribution at 24 h was used to confirm the uptake values, and tumors were visualized by post-mortem fluorescence imaging. Results: A11 cMb-Cy5.5 retained low nanomolar affinity for PSCA-positive cells. Conjugation conditions were established (dye-to-protein ratio of 0.7:1) that did not affect the biodistribution, pharmacokinetics, or clearance of A11 cMb. ImmunoPET using dual-labeled 124I-A11 cMb-Cy5.5 showed specific targeting to both 22Rv1-PSCA and PC3-PSCA s.c. xenografts in nude mice. Ex vivo biodistribution confirmed specific uptake to PSCA-expressing tumors with 22Rv1-PSCA:22Rv1 and PC3-PSCA:PC3 ratios of 13:1 and 5.6:1, respectively. Consistent with the immunoPET, fluorescence imaging showed a strong signal from both 22Rv1-PSCA and PC3-PSCA tumors compared with non-PSCA expressing tumors. In an orthotopic model, 89Zr-A11 cMb-Cy5.5 immunoPET was able to detect intraprostatically implanted 22Rv1-PSCA cells. Importantly, fluorescence imaging clearly distinguished the prostate tumor from surrounding seminal vesicles. Conclusion: Dual-labeled A11 cMb specifically visualized PSCA-positive tumor by successive immunoPET/fluorescence, which can potentially be translated for preoperative whole-body prostate cancer detection and intraoperative surgical guidance in patients.
关键词: molecular imaging,immunoPET,prostate cancer,antibody fragment,fluorescence
更新于2025-09-23 15:22:29
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Synthesis and preclinical evaluation of 68Ga-PSMA-BCH for prostate cancer imaging
摘要: Prostate specific membrane antigen (PSMA) is a promising target for the diagnosis and therapy of prostate cancer. In this report, a NOTA-conjugated precursor, NOTA-PSMA (also named PSMA-BCH), was synthesized by peptide synthesizer with the chemical purity over 95%. 68Ga-PSMA-BCH was obtained by radiolabeling NOTA-PSMA with 68GaCl3 with >99% radiochemical purity and 59-74 GBq/μmol specific activity. In vitro and in vivo study of 68Ga-PSMA-BCH showed high stability, high uptake in PSMA-expressing cells and tumor, fast clearance and low non-target uptake. 22Rv1 tumors were clearly observed in micro-PET images of and showed good retention. Compared with 68Ga-PSMA-617, 68Ga-PSMA-BCH showed comparable tumor uptake and tumor-background ratios. Indicating 68Ga-PSMA-BCH is a promising candidate for prostate cancer imaging and worthy of further clinical investigations.
关键词: 68Ga-PSMA-BCH,PSMA,PET imaging,Prostate cancer
更新于2025-09-23 15:22:29
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Technical notes Integrated image navigation system using head-mounted display in “RoboSurgeon” endoscopic radical prostatectomy
摘要: The safety and efficacy of minimally invasive surgery relies on visual information. We aimed to develop an integrated image navigation system (RoboSurgeon System) that combines head-mounted displays (HMDs) with multiple image modalities, and assessed its feasibility in 5 prostate cancer patients who underwent gasless single-port endoscopic radical prostatectomy. A robotically manipulated transrectal ultrasound (TRUS) system was used. In all cases, preoperative magnetic resonance (MR) images and intraoperative real-time images of an endoscope, TRUS, and HMD-mounted camera were integrated and displayed synchronously on each HMD in a four-split screen mode during the entire process. The TRUS helped identify the boundary with the adjacent structures endoscopically in reference to MR images. There were no negative incidents in intraoperative or postoperative courses. Integrated image navigation using HMDs as individualized monitors is feasible in the natural ergonomic position and may be beneficial to identify correct dissection planes. The efficacy of the RoboSurgeon System deserves further evaluation.
关键词: image navigation,prostate cancer,head-mounted display,minimally invasive surgery,transrectal ultrasound,radical prostatectomy
更新于2025-09-23 15:22:29
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Synthesis and Evaluation of Multifunctional Fluorescent Inhibitors with Synergistic Interaction of PSMA and Hypoxia for Prostate Cancer
摘要: Prostate cancer is one of the most common cancers in the world. It is widely known that prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer, and hypoxia is a common characteristic of many solid tumors, including prostate cancer. In this study, we designed multifunctional fluorescent inhibitors to target PSMA and tumor hypoxia in order to increase the tumor uptake of inhibitors. Novel PSMA inhibitors were prepared using lysine as the backbone to connect three different functional groups: the glutamate-urea-lysine (GUL) structure for inhibiting PSMA, 2-nitroimidazole for the hypoxia-sensitive moiety, and a near-infrared fluorophore (sulfo-Cyanine 5.5). According to the in vitro PSMA binding assay, novel fluorescent inhibitors were demonstrated to have nanomolar binding affinities. Multifunctional inhibitor 2 with one 2-nitroimidazole had a similar inhibitory activity to inhibitor 1 that did not contain the hypoxia targeting moiety, but multifunctional inhibitor 3 with two 2-nitroimidazoles showed lower inhibitory activity than inhibitor 1 due to the bulky structure of the hypoxia-sensitive group. However, in vivo optical imaging and ex vivo biodistribution studies indicated that both multifunctional inhibitors 2 and 3 had higher accumulation in tumors than inhibitor 1 due to a synergistic combination of PSMA and hypoxia targeting moieties. These observations suggest that this novel multifunctional strategy might be a promising approach to improve the diagnosis and therapy of prostate cancer.
关键词: multifunctional inhibitors,hypoxia,near-infrared fluorophore,Prostate cancer,2-nitroimidazole,PSMA
更新于2025-09-23 15:21:21
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The near-infrared fluorescent dye IR-780 was coupled with cabazitaxel for castration-resistant prostate cancer imaging and therapy
摘要: A new drug, Caba-780, was synthesized by chemical coupling of the heptamethyl phthalocyanine near-infrared fluorescent (NIRF) dye IR-780 and the paclitaxel-based chemotherapeutic drug cabazitaxel. Then, the potential value of Caba-780 in the diagnosis and treatment of castration-resistant prostate cancer (CRPC) was evaluated. The CRPC cell lines DU145 and PC-3, as well as the normal human prostate stromal cell line WPMY-1, were used to evaluate the uptake of Caba-780 and its antitumor effect in vitro. The distribution, antitumor effect, and safety of Caba-780 were also evaluated in tumor-bearing mouse xenograft models. Our results showed that Caba-780 was efficiently absorbed by DU145 and PC-3 cells and that the cytotoxicity of Caba-780 was significantly stronger than that of IR-780 and cabazitaxel. In addition, Caba-780 inhibited the migration and invasion of DU145 and PC-3 cells and promoted apoptosis by prolonging the G2 phase of the cell cycle. Further analysis indicated that Caba-780 could be used to effectively image tumor xenografts. At the same time, this drug inhibited the growth of tumors in vivo. Therefore, the new synthetic drug Caba-780 has potential applications in the diagnosis and treatment of CRPC.
关键词: Organic anion-transporting polypeptide,Chemotherapy,Castration-resistant prostate cancer,Near-infrared fluorescent dye
更新于2025-09-23 15:21:01
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[IEEE 2019 Conference on Lasers and Electro-Optics Europe & European Quantum Electronics Conference (CLEO/Europe-EQEC) - Munich, Germany (2019.6.23-2019.6.27)] 2019 Conference on Lasers and Electro-Optics Europe & European Quantum Electronics Conference (CLEO/Europe-EQEC) - Probing Neuronal Activity using Membrane Interfacial Water
摘要: The use of high-volume quantitative radiomics features extracted from multi-parametric magnetic resonance imaging (MP-MRI) is gaining attraction for the autodetection of prostate tumors, since it provides a plethora of mineable data, which can be used for both detection and prognosis of prostate cancer. While current voxel-resolution radiomics-driven prostate tumor detection approaches utilize quantitative radiomics features associated with individual voxels on an independent basis, the incorporation of additional information regarding the spatial and radiomics feature relationships between voxels has significant potential for achieving a more reliable detection performance. Motivated by this, we present a novel approach for automatic prostate cancer detection using a radiomics-driven conditional random field (RD-CRF) framework. In addition to the high-throughput extraction and utilization of a comprehensive set of voxel-level quantitative radiomics features, the proposed RD-CRF framework leverages inter-voxel spatial and radiomics feature relationships to ensure that the autodetected tumor candidates exhibit interconnected tissue characteristics reflective of cancerous tumors. We evaluated the performance of the proposed framework using clinical prostate MP-MRI data of 20 patients, and the results of RD-CRF framework demonstrated a clear improvement with respect to the state-of-the-art in quantitative radiomics for automatic voxel-resolution prostate cancer detection.
关键词: multi-parametric magnetic resonance imaging (MP-MRI),Automatic prostate cancer detection,radiomics,feature model,conditional random fields (CRF)
更新于2025-09-23 15:21:01
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Improved repeatability of dynamic contrast-enhanced MRI using the complex MRI signal to derive arterial input functions: a test-retest study in prostate cancer patients
摘要: Purpose: The arterial input function (AIF) is a major source of uncertainty in tracer kinetic (TK) analysis of dynamic contrast‐enhanced (DCE)‐MRI data. The aim of this study was to investigate the repeatability of AIFs extracted from the complex signal and of the resulting TK parameters in prostate cancer patients. Methods: Twenty‐two patients with biopsy‐proven prostate cancer underwent a 3T MRI exam twice. DCE‐MRI data were acquired with a 3D spoiled gradient echo sequence. AIFs were extracted from the magnitude of the signal (AIFMAGN), phase (AIFPHASE), and complex signal (AIFCOMPLEX). The Tofts model was applied to extract Ktrans, kep and ve. Repeatability of AIF curve characteristics and TK parameters was assessed with the within‐subject coefficient of variation (wCV). Results: The wCV for peak height and full width at half maximum for AIFCOMPLEX (7% and 8%) indicated an improved repeatability compared to AIFMAGN (12% and 12%) and AIFPHASE (12% and 7%). This translated in lower wCV values for Ktrans (11%) with AIFCOMPLEX in comparison to AIFMAGN (24%) and AIFPHASE (15%). For kep, the wCV was 16% with AIFMAGN, 13% with AIFPHASE, and 13% with AIFCOMPLEX. Conclusion: Repeatability of AIFPHASE and AIFCOMPLEX is higher than for AIFMAGN, resulting in a better repeatability of TK parameters. Thus, use of either AIFPHASE or AIFCOMPLEX improves the robustness of quantitative analysis of DCE‐MRI in prostate cancer.
关键词: arterial input function,dynamic contrast‐enhanced MRI,repeatability,prostate cancer,tracer kinetic analysis,complex signal
更新于2025-09-19 17:15:36