- 标题
- 摘要
- 关键词
- 实验方案
- 产品
-
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
-
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
-
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
-
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
-
Discovery of [ <sup>18</sup> F]PSMA-7, a novel PET-probe for the detection of small PSMA positive lesions
摘要： Prostate specific membrane antigen (PSMA) expressed by the vast majority of prostate cancers (PCa) is a promising target for PCa imaging. The application of PSMA specific 18F-labeled PET probes like 18F-DCFPyL and 18F-PSMA-1007 considerably improved the accuracy of PCa tumor detection. However, there remains a need for further improvements regarding sensitivity and specificity. The aim of this study was the development of highly selective and specific PSMA probes with enhanced imaging properties, in comparison with 18F-DCFPyL, 18F-PSMA-1007 and 68Ga-PSMA-11. Methods: Eight novel 18F-labeled PSMA ligands were prepared. Their cellular uptake in PSMA+ LNCaP C4-2 and PSMA– PC-3 cells was compared to that of 18F-DCFPyL. The most promising candidates were additionally evaluated by μPET in healthy rats using PSMA+ peripheral ganglia as a model for small PCa lesions. PET images of the ligand with the best outcome, 18F-JK-PSMA-7, were compared to those of 18F-DCFPyL, 18F-PSMA-1007 and 68Ga-PSMA-11 with respect to key image quality parameters for the time frame 60-120 min. Results: Compared to 18F-DCFPyL, 18F-JK-PSMA-7 demonstrated increased PSMA specific cellular uptake. While target-to-background ratios of 18F-DCFPyL and 18F-PSMA-1007 were comparable, this parameter was higher for 18F-JK-PSMA-7 and lower for 68Ga-PSMA-11. Image acutance was significantly higher for 18F-JK-PSMA-7 and 18F-PSMA-1007 compared to 18F-DCFPyL and 68Ga-PSMA-11. Image resolution was similar for all four tracers. 18F-PSMA-1007 demonstrated significantly higher blood protein binding and bone uptake than the other tracers. Conclusion: 18F-JK-PSMA-7 is a promising candidate for high quality visualization of small PSMA-positive lesions. Excellent preclinical imaging properties justify further preclinical and clinical studies of this tracer.
关键词： Prostate carcinoma,PSMA,preclinical model,radiofluorination,positron emission tomography,imaging
更新于2025-09-23 15:21:01
-
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
-
Assessment of 68Ga-PSMA-11 PET positivity predictive factors in prostate cancer
摘要： Purpose: Positron emission tomography (PET) studies with 68Ga-PSMA-11 (68Ga-HBED-CC-PSMA) have earned the attention of researchers, due to overexpression of PSMA in the tumoral tissues of prostate cancer. Our aim was to analyze the potential benefit of this radiotracer in the biochemical relapse of prostate cancer. Material and methods: This retrospective analysis included 53 studies, performed on 50 male prostate cancer patients referred due to biochemical recurrence. In all cases, previous imaging techniques were negative or inconclusive. Results: Of the 53 studies, 36 (68%) were positive. Significant differences were found between the positive and negative PET groups in Gleason’s scale, PSA levels, PSAdt, late acquisition and the administration of androgen deprivation therapy during treatment (p < .05). Regarding PSA levels, 10 (48%) of the 21 patients with PSA < 1 ng/ml, obtained a pathological PET result. When the PSAdt was below six months, 86.7% of the patients obtained an abnormal PET. In the multivariate analysis, only Gleason’s scale was associated independently with an abnormal PET result. Conclusions: 68Ga-PSMA-11 PET shows a high disease detection rate in patients where other techniques showed negative or doubtful images. Almost 50% of patients with prostate cancer biochemical recurrence and low PSA levels (<1 ng/ml) have active disease on 68Ga-PSMA-11 PET, precisely where other radiotracers lack sensitivity.
关键词： Prostate-specific membrane antigen,68Ga-PSMA-11,Prostate cancer,Positron emission tomography
更新于2025-09-09 09:28:46
-
Comparison of [68Ga]Ga-PSMA-HBED-CC PET versus Whole-Body Bone Scintigraphy for the Detection of Bone Metastases in Patients with Prostate Cancer
摘要： Aim: To compare [68Ga]Ga-PSMA-HBED-CC PET and (99m)Tc-DPD bone scintigraphy for the detection of bone metastases from prostate cancer. Methods: [68Ga]Ga-PSMA-HBED-CC PET/CT and (99m)Tc-DPD bone scintigraphy in 19 men with histopathological proven prostate cancer were compared to each other for the sensitivity/specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) for the detection of bone metastases. Results: According to the standard of reference lesion-based analysis of [68Ga]Ga-PSMA-HBED-CC PET and (99m)Tc-DPD bone scintigraphy reached a sensitivity of 45.6%/34%, specificity of 86.4%/81.4%, accuracy of 60.5%/51.2%, positive predictive value of 85.5%/76.1%, and negative predictive value of 47.7%/41.4%, respectively. Conclusion: [68Ga]Ga-PSMA-HBED-CC PET could detect significantly more bone metastases in prostate cancer than (99m)Tc-DPD bone scintigraphy.
关键词： Bone metastases,Prostate cancer,(99m)Tc-DPD scintigraphy,[68Ga]Ga HBED-CC PSMA,Detection rate
更新于2025-09-09 09:28:46
-
SERS-Based Quantification of PSMA in Tissue Microarrays Allows Effective Stratification of Patients with Prostate Cancer
摘要： Prostate specific membrane antigen (PSMA), a type II membrane protein, is an attractive biomarker that has been validated clinically for the diagnosis of prostate cancer. In this study, we developed surface-enhanced Raman scattering (SERS) nanoprobes for PSMA detection and quantification at the single-cell level on prostate cancer cells. The cells were targeted employing SERS nanoprobes that consisted of gold nanostars functionalized with PSMA aptamer molecules. We were able to quantify picomolar concentrations of soluble PSMA protein and used the resulting calibration curve to estimate the expression of PSMA on the surface of the prostate cancer cell, LNCaP, at the single-cell level. Importantly, we employed these SERS tags to stratify prostate cancer patients by assessing PSMA expression in tissues contained in a prostate tissue microarray. The stratification results clearly correlated PSMA expression to recommended therapy groups, rendering the described method as an effective tool to aid in designing personalized therapeutic protocols. Benchmarking detection sensitivity against immunofluorescence staining and comparing stratification results obtained with the two methods allowed us to validate our novel approach against standard practices. On the basis of these results, we confirm the validity of PSMA as an effective biomarker for prostate cancer patient evaluation and propose SERS-based diagnostic techniques as integrative methods for the assessment of disease stage and the identification of effective therapeutic protocols.
关键词： aptamer,tissue microarray,surface-enhanced Raman scattering,PSMA,Prostate specific membrane antigen,SERS,nanoprobes,prostate cancer,biomarker,gold nanostars
更新于2025-09-04 15:30:14