End-to-end [18F]PSMA-1007 PET/CT radiomics-based pipeline for predicting ISUP grade group in prostate cancer.

OBJECTIVES: To develop an end-to-end radiomics-based pipeline for the prediction of International Society of Urological Pathology grade group (ISUP GG) in prostate cancer (PCa). METHODS: This retrospective study includes 356 patients (241 in training set and 115 in independent test set) with histopathologically confirmed PCa who underwent [18F]PSMA-1007 PET/CT scan. Patients were classified into two groups according to their ISUP GG (1-3 vs. 4-5). Radiomics features were extracted from the whole, automatically segmented prostate on PET/CT images, 30 models were constructed by combining 6 feature selection algorithms and 5 machine learning classifiers. The clinical model incorporated age, total prostate-specific antigen (tPSA), maximum standardized uptake value (SUVmax), and prostate volume. The predictive performance of the models was evaluated using the area under the receiver operating characteristic curve (AUC), balanced accuracy (bAcc), and decision curve analysis (DCA). RESULTS: The best-performing radiomics model significantly outperformed clinical model (AUC 0.879 ± 0.041 vs. 0.799 ± 0.051, bAcc 0.745 ± 0.074 vs. 0.629 ± 0.045). On an external independent test set, best-performing radiomics model perform better than clinical model, with an AUC of 0.861 vs. 0.750, p = 0.002 (Delong), and bAcc of 0.764 vs. 0.582, p = 0.043 (McNemar). The learning curve, calibration curve and DCA demonstrated goodness-of-fit and improved benefits in clinical practice. CONCLUSION: The end-to-end radiomics-based pipeline is an effective non-invasive tool to predict ISUP GG in PCa.

A Robust [18F]-PSMA-1007 Radiomics Ensemble Model for Prostate Cancer Risk Stratification.

The aim of this study is to investigate the role of [18F]-PSMA-1007 PET in differentiating high- and low-risk prostate cancer (PCa) through a robust radiomics ensemble model. This retrospective study included 143 PCa patients who underwent [18F]-PSMA-1007 PET/CT imaging. PCa areas were manually contoured on PET images and 1781 image biomarker standardization initiative (IBSI)-compliant radiomics features were extracted. A 30 times iterated preliminary analysis pipeline, comprising of the least absolute shrinkage and selection operator (LASSO) for feature selection and fivefold cross-validation for model optimization, was adopted to identify the most robust features to dataset variations, select candidate models for ensemble modelling, and optimize hyperparameters. Thirteen subsets of selected features, 11 generated from the preliminary analysis plus two additional subsets, the first based on the combination of robust and fine-tuning features, and the second only on fine-tuning features were used to train the model ensemble. Accuracy, area under curve (AUC), sensitivity, specificity, precision, and f-score values were calculated to provide models' performance. Friedman test, followed by post hoc tests corrected with Dunn-Sidak correction for multiple comparisons, was used to verify if statistically significant differences were found in the different ensemble models over the 30 iterations. The model ensemble trained with the combination of robust and fine-tuning features obtained the highest average accuracy (79.52%), AUC (85.75%), specificity (84.29%), precision (82.85%), and f-score (78.26%). Statistically significant differences (p < 0.05) were found for some performance metrics. These findings support the role of [18F]-PSMA-1007 PET radiomics in improving risk stratification for PCa, by reducing dependence on biopsies.

A comparative study of 18F-PSMA-1007 PET/CT and pelvic MRI in newly diagnosed prostate cancer.

PURPOSE: To evaluate the difference in the diagnostic efficacy of 18F-PSMA-1007 PET/CT and pelvic MRI in primary prostate cancer, as well as the correlation between the two methods and histopathological parameters and serum PSA levels. METHODS: A total of 41 patients with suspected prostate cancer who underwent 18F-PSMA-1007 PET/CT imaging in our department from 2018 to 2023 were retrospectively collected. All patients underwent 18F-PSMA-1007 PET/CT and MRI scans. The sensitivity, PPV and diagnostic accuracy of MRI and 18F-PSMA-1007 PET/CT in the diagnosis of prostate cancer were calculated after comparing the results of MRI and 18F-PSMA-1007 PET/CT with biopsy. The Spearman test was used to calculate the correlation between 18F-PSMA-1007 PET/CT, MRI parameters, histopathological indicators, and serum PSA levels. RESULTS: Compared with histopathological results, the sensitivity, PPV and diagnostic accuracy of 18F-PSMA-1007 PET/CT in the diagnosis of prostate cancer were 95.1%, 100.0% and 95.1%, respectively. The sensitivity, PPV and diagnostic accuracy of MRI in the diagnosis of prostate cancer were 82.9%, 100.0% and 82.9%, respectively. There was a mild to moderately positive correlation between Gleason (Gs) score, Ki-67 index, serum PSA level and 18F-PSMA-1007 PET/CT parameters (p < 0.05). There was a moderately negative correlation between the expression of AMACR (P504S) and 18F-PSMA-1007 PET/CT parameters (p < 0.05). The serum PSA level and the Gs score were moderately positively correlated with the MRI parameters (p < 0.05). There was no correlation between histopathological parameters and MRI parameters (p > 0.05). CONCLUSION: Compared with MRI, 18F-PSMA-1007 PET/CT has higher sensitivity and diagnostic accuracy in the detection of malignant prostate tumors. In addition, the Ki-67 index and AMACR (P504S) expression were only correlated with 18F-PSMA-1007 PET/CT parameters. Gs score and serum PSA level were correlated with 18F-PSMA-1007 PET/CT and MRI parameters. 18F-PSMA-1007 PET/CT examination can provide certain reference values for the clinical diagnosis, evaluation, and treatment of malignant prostate tumors.

A tumor-like renal arteriovenous malformation on 18F-PSMA-1007 PET/CT: a case report.

Background: Renal arteriovenous malformations (rAVMs) are congenital abnormal pathways between renal arteries and veins that are rare in the general population. It is often misdiagnosed as malignant renal tumors with abundant blood supply, and the definitive diagnosis primarily relies on angiography. Multimodality imaging, including contrast-enhanced computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT plays an important role in the differential diagnosis of renal space-occupying lesions. Case presentation: A 56-year-old man presented with abdominal distension, loss of appetite, and back pain without obvious cause 2 years ago, without nausea vomiting, or frequent urination. Gastroscopy and colonoscopy showed multiple polyps in the duodenum and colon. Abdomen contrast-enhanced CT revealed a mass of 1.6 × 1.4 cm in the left kidney, which was considered to be a malignant tumor. PET/CT was performed for further diagnosis; the 18F-fluorodesoxyglucose (18F-FDG) PET/CT scan showed mild uptake in the left renal mass, while no uptake of 18F- prostate-specific membrane antigen (PSMA) was observed. Following a multidisciplinary discussion, the possibility of renal AVMs was considered and subsequently confirmed by renal angiography as the diagnosis. Then, selective segmental renal artery embolization was performed for treatment. Conclusion: Renal AVMs are extremely rare in clinical practice. Due to limited research on the application of 18F-FDG and 18F-PSMA PET/CT to renal AVMs, its role remains largely unexplored. With the increasing popularity of PET/CT imaging, comprehensive imaging of the disease has become indispensable. We report the first case of PSMA PET/CT imaging in renal AVMs, and when PSMA expression is absent in a renal mass, the possibility of renal AVMs should be considered.

Prostate-specific Membrane Antigen: Diagnostics.

Since its clinical introduction in May 2011, prostate-specific membrane antigen (PSMA)-PET/computed tomography has quickly gained worldwide recognition as a significant breakthrough in prostate cancer diagnostics. In the meantime, several new PSMA radioligands for PET imaging have been introduced into routine clinical practice. This article aims to introduce the most commonly used tracers and their key areas of application.

Development and validation of [18 F]-PSMA-1007 PET-based radiomics model to predict biochemical recurrence-free survival following radical prostatectomy.

PURPOSE: Biochemical recurrence (BCR) following radical prostatectomy (RP) is a significant concern for patients with prostate cancer. Reliable prediction models are needed to identify patients at risk for BCR and facilitate appropriate management. This study aimed to develop and validate a clinical-radiomics model based on preoperative [18 F]PSMA-1007 PET for predicting BCR-free survival (BRFS) in patients who underwent RP for prostate cancer. MATERIALS AND METHODS: A total of 236 patients with histologically confirmed prostate cancer who underwent RP were retrospectively analyzed. All patients had a preoperative [18 F]PSMA-1007 PET/CT scan. Radiomics features were extracted from the primary tumor region on PET images. A radiomics signature was developed using the least absolute shrinkage and selection operator (LASSO) Cox regression model. The performance of the radiomics signature in predicting BRFS was assessed using Harrell's concordance index (C-index). The clinical-radiomics nomogram was constructed using the radiomics signature and clinical features. The model was externally validated in an independent cohort of 98 patients. RESULTS: The radiomics signature comprised three features and demonstrated a C-index of 0.76 (95% CI: 0.60-0.91) in the training cohort and 0.71 (95% CI: 0.63-0.79) in the validation cohort. The radiomics signature remained an independent predictor of BRFS in multivariable analysis (HR: 2.48, 95% CI: 1.47-4.17, p < 0.001). The clinical-radiomics nomogram significantly improved the prediction performance (C-index: 0.81, 95% CI: 0.66-0.95, p = 0.007) in the training cohort and (C-index: 0.78 95% CI: 0.63-0.89, p < 0.001) in the validation cohort. CONCLUSION: We developed and validated a novel [18 F]PSMA-1007 PET-based clinical-radiomics model that can predict BRFS following RP in prostate cancer patients. This model may be useful in identifying patients with a higher risk of BCR, thus enabling personalized risk stratification and tailored management strategies.

Prognostic Performance of RECIP 1.0 Based on [18F]PSMA-1007 PET in Prostate Cancer Patients Treated with [177Lu]Lu-PSMA I&T.

In metastatic castration-resistant prostate cancer (mCRPC) patients treated with prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), the recently proposed criteria for evaluating response to PSMA PET (RECIP 1.0) based on 68Ga- and 18F-labeled PET agents provided prognostic information in addition to changes in prostate-specific antigen (PSA) levels. Our aim was to evaluate the prognostic performance of this framework for overall survival (OS) in patients undergoing RLT and imaged with [18F]PSMA-1007 PET/CT and compare the prognostic performance with the PSA-based response assessment. Methods: In total, 73 patients with mCRPC who were scanned with [18F]PSMA-1007 PET/CT before and after 2 cycles of RLT were retrospectively analyzed. We calculated the changes in serum PSA levels (ΔPSA) and quantitative PET parameters for the whole-body tumor burden (SUVmean, SUVmax, PSMA tumor volume, and total lesion PSMA). Men were also classified following the Prostate Cancer Working Group 3 (PCWG3) criteria for ΔPSA and RECIP 1.0 for PET imaging response. We performed univariable Cox regression analysis, followed by multivariable and Kaplan-Meier analyses. Results: Median OS was 15 mo with a median follow-up time of 14 mo. Univariable Cox regression analysis provided significant associations with OS for ΔPSA (per percentage, hazard ratio [HR], 1.004; 95% CI, 1.002-1.007; P < 0.001) and PSMA tumor volume (per unit, HR, 1.003; 95% CI, 1.000-1.005; P = 0.03). Multivariable Cox regression analysis confirmed ΔPSA (per percentage, HR, 1.004; 95% CI, 1.001-1.006; P = 0.006) as an independent prognosticator for OS. Kaplan-Meier analyses provided significant segregation between individuals with versus those without any PSA response (19 mo vs. 14 mo; HR, 2.00; 95% CI, 0.95-4.18; P = 0.04). Differentiation between patients with or without progressive disease (PD) was also feasible when applying PSA-based PCWG3 (19 mo vs. 9 mo for non-PD and PD, respectively; HR, 2.29; 95% CI, 1.03-5.09; P = 0.01) but slightly failed when applying RECIP 1.0 (P = 0.08). A combination of both response systems (PCWG3 and RECIP 1.0), however, yielded the best discrimination between individuals without versus those with PD (19 mo vs. 8 mo; HR, 2.78; 95% CI, 1.32-5.86; P = 0.002). Conclusion: In patients with mCRPC treated with RLT and imaged with [18F]PSMA-1007, frameworks integrating both the biochemical (PCWG3) and PET-based response (RECIP 1.0) may best assist in identifying subjects prone to disease progression.

Agreement between PSMA-RADS and E-PSMA systems in classifying [18F]PSMA-1007 PET/CT lesions among prostate cancer patients: exploring the correlation between lesion size and uptake.

Purpose: To determine the agreement between the PSMA-RADS and E-PSMA standardized reporting systems in the classification of [18F]PSMA-1007-uptaking lesions identified on PET/CT scan in patients with prostate cancer (PCa) and post-prostatectomy with suspected recurrent disease (local recurrence, regional nodal involvement and distant metastases), based on biochemical recurrence, while also exploring the correlation between lesion size and tracer uptake. Materials and methods: A retrospective cross-sectional study of 32 post-prostatectomy PCa patients who had suspected recurrent disease based on biochemical recurrence post-prostatectomy (prostate-specific antigen values that are 0.2 ng/mL or higher) underwent [18F]PSMA-1007 PET/CT scan. The recurrent disease PCa lesions were characterized and subsequently classified using two standardized reporting systems (PSMA-RADS and E-PSMA). The lesions were grouped based on anatomical site, their size and SUVmax were compared using Kruskal-Wallis test with Dunn-Bonferroni post hoc tests. Spearman correlation coefficients were calculated between the size of the lesions and their SUVmax of the radiotracer [18F]PSMA-1007 for all the lesions and when grouped by anatomical site. Additionally, the agreement between lesion classifications was assessed using Cohen's kappa index. Results: Only 32 (69.98 ± 8.27, men) patients met the inclusion criteria, a total of 149 lesions with avid uptake of [18F]PSMA-1007 were identified. Positive correlation (r = 0.516, p < 0.001) was observed between the size of the metastatic prostate cancer lymph node lesions and their [18F]PSMA-1007 uptake. Substantial agreement was noted between the PSMA-RADS and E-PSMA classification system scores among all lesions (κ = 0.70, p < 0.001), with notable discrepancies primarily among lymph node lesions. Conclusion: Our findings revealed a positive correlation between the size of the metastatic prostate cancer lymph node lesions and [18F]PSMA-1007 uptake, and although there was substantial agreement between the PSMA-RADS and E-PSMA classification systems, there were discrepancies mainly among the lymph node lesions.

Predictive value of volumetric parameters based on 18F-PSMA-1007 PET/CT for prostate cancer metastasis.

Purpose of the report: To explore the value of 18F-labeled prostate-specific membrane antigen (PSMA-1007) positron emission tomography (PET)/computed tomography (CT), the maximum standardized uptake value (SUVmax) of the primary tumor, prostate PSMA-tumor volume (PSMA-TVp), and prostate total lesion PSMA (TL-PSMAp) for predicting prostate cancer (PCa) metastasis and follow-up evaluation in primary PCa lesions. Materials and methods: 18F-PSMA-1007 PET/CT data of 110 consecutive newly diagnosed PCa patients were retrospectively analyzed. Patients were divided into non-metastatic, oligometastatic, and extensive metastatic groups. The predictive power was assessed using the receiver operating characteristic curve. Multi-group one-way analysis of variance and post-hoc tests were used to compare the groups. Patients were monitored post-therapy to evaluate treatment effectiveness. Results: Among the 110 patients, 66.4% (73) had metastasis (29 oligometastatic, 44 extensive metastasis). AUCs for Gleason score (GS), total prostate-specific antigen(TPSA), SUVmax, TL-PSMAp, and PSMA-TVp were 0.851, 0.916, 0.834, 0.938, and 0.923, respectively. GS, TPSA, SUVmax, TL-PSMAp, and PSMA-TVp were significantly different among the groups. In the post-hoc tests, differences in GS, TPSA, SUVmax, TL-PSMAp, and PSMA-TVp between the non-metastatic and oligometastatic groups and non-metastatic and extensive metastatic groups were significant (P<0.010). Differences in TL-PSMAp and PSMA-TVp between oligometastatic and extensive metastatic groups were significant (P=0.039 and 0.015, respectively), while those among GS, TPSA, and SUVmax were not. TL-PSMAp and PSMA-TVp distinguished between oligometastatic and extensive metastases, but GS, TPSA, and SUVmax did not. In individuals with oligometastasis, the implementation of active treatment for both primary and metastatic lesions may result in a more favorable prognosis. Conclusions: 18F-PSMA-1007 PET/CT volumetric parameters PSMA-TVp and TL-PSMAp can predict PCa oligometastasis.

Multimodal radiomics based on 18F-Prostate-specific membrane antigen-1007 PET/CT and multiparametric MRI for prostate cancer extracapsular extension prediction.

OBJECTIVES: To compare the performance of the multiparametric magnetic resonance imaging (mpMRI) radiomics and 18F-Prostate-specific membrane antigen (PSMA)-1007 PET/CT radiomics model in diagnosing extracapsular extension (EPE) in prostate cancer (PCa), and to evaluate the performance of a multimodal radiomics model combining mpMRI and PET/CT in predicting EPE. METHODS: We included 197 patients with PCa who underwent preoperative mpMRI and PET/CT before surgery. mpMRI and PET/CT images were segmented to delineate the regions of interest and extract radiomics features. PET/CT, mpMRI, and multimodal radiomics models were constructed based on maximum correlation, minimum redundancy, and logistic regression analyses. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and indices derived from the confusion matrix. RESULTS: AUC values for the mpMRI, PET/CT, and multimodal radiomics models were 0.85 (95% CI, 0.78-0.90), 0.73 (0.64-0.80), and 0.83 (0.75-0.89), respectively, in the training cohort and 0.74 (0.61-0.85), 0.62 (0.48-0.74), and 0.77 (0.64-0.87), respectively, in the testing cohort. The net reclassification improvement demonstrated that the mpMRI radiomics model outperformed the PET/CT one in predicting EPE, with better clinical benefits. The multimodal radiomics model performed better than the single PET/CT radiomics model (P < .05). CONCLUSION: The mpMRI and 18F-PSMA-PET/CT combination enhanced the predictive power of EPE in patients with PCa. The multimodal radiomics model will become a reliable and robust tool to assist urologists and radiologists in making preoperative decisions. ADVANCES IN KNOWLEDGE: This study presents the first application of multimodal radiomics based on PET/CT and MRI for predicting EPE.

Combined whole-body dynamic and static PET/CT with low-dose [18F]PSMA-1007 in prostate cancer patients.

AIM: In addition to significant improvements in sensitivity and image quality, the recent introduction of long axial field-of-view (LAFOV) PET/CT scanners has enabled dynamic whole-body imaging for the first time. We aim herein to determine an appropriate acquisition time range for static low-dose [18F]PSMA-1007 PET imaging and to investigate the whole-body pharmacokinetics of [18F]PSMA-1007 by dynamic PET with the LAFOV Biograph Vision Quadra PET/CT in a group of prostate cancer patients. METHODOLOGY: In total, 38 prostate cancer patients were enrolled in the analysis for staging or re-staging purposes. Thirty-four patients underwent dynamic whole-body PET/CT (60 min) followed by static whole-body PET/CT and four patients underwent static whole-body PET/CT only. The activity applied was 2 MBq/kg [18F]PSMA-1007. The static PET images of 10-min duration (PET-10) were reconstructed and further split into 8-min (PET-8), 6-min (PET-6), 5-min (PET-5), 4-min (PET-4), and 2-min (PET-2) duration groups. Comparisons were made between the different reconstructed scan times in terms of lesion detection rate and image quality based on SUV calculations of tumor lesions and the spleen, which served as background. Analysis of the dynamic PET/CT data was based on a two-tissue compartment model using an image-derived input function obtained from the descending aorta. RESULTS: Analysis of lesion detection rate showed no significant differences when reducing PET acquisitions from 10 up to 5 min. In particular, a total of 169 lesions were counted with PET-10, and the corresponding lesion detection rates (95% CI for the 90% quantile of the differences in tumor lesions) for shorter acquisitions were 100% (169/169) for PET-8 (95% CI: 0-0), 98.8% (167/169) for PET-6 (95% CI: 0-1), 95.9% (162/169) for PET-5 (95% CI: 0-3), 91.7% (155/169) for PET-4 (95% CI: 1-2), and 85.2% (144/169) for PET-2 (95% CI: 1-6). With the exception of PET-2, the differences observed between PET-10 and the other shorter acquisition protocols would have no impact on any patient in terms of clinical management. Objective evaluation of PET/CT image quality showed no significant decrease in tumor-to-background ratio (TBR) with shorter acquisition times, despite a gradual decrease in signal-to-noise ratio (SNR) in the spleen. Whole-body quantitative [18F]PSMA-1007 pharmacokinetic analysis acquired with full dynamic PET scanning was feasible in all patients. Two-tissue compartment modeling revealed significantly higher values for the parameter k3 in tumor lesions and parotid gland compared to liver and spleen, reflecting a higher specific tracer binding to the PSMA molecule and internalization rate in these tissues, a finding also supported by the respective time-activity curves. Furthermore, correlation analysis demonstrated a significantly strong positive correlation (r = 0.72) between SUV and k3 in tumor lesions. CONCLUSIONS: In prostate cancer, low-dose (2 MBq/kg) [18F]PSMA-1007 LAFOV PET/CT can reduce static scan time by 50% without significantly compromising lesion detection rate and objective image quality. In addition, dynamic PET can elucidate molecular pathways related to the physiology of [18F]PSMA-1007 in both tumor lesions and normal organs at the whole-body level. These findings unfold many of the potentials of the new LAFOV PET/CT technology in the field of PSMA-based diagnosis and theranostics of prostate cancer.

Combination of [18F]FDG and [18F]PSMA-1007 PET/CT predicts tumour aggressiveness at staging and biochemical failure postoperatively in patients with prostate cancer.

PURPOSE: [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) has limitations in prostate cancer (PCa) detection owing to low glycolysis in the primary tumour. Recently, prostate-specific membrane antigen (PSMA) PET/CT has been useful for biochemical failure detection and radioligand therapy (RLT) guidance. However, few studies have evaluated its use in primary prostate tumours using PSMA and [18F]FDG PET/CT. This study aimed to evaluate [18F]PSMA-1007 and [18F]FDG PET/CT for primary tumour detection and understand the association of metabolic heterogeneity with clinicopathological characteristics at staging and postoperatively. METHOD: This prospective study included 42 index tumours (27 acinar and 15 ductal-dominant) in 42 patients who underwent [18F]PSMA-1007 and [18F]FDG PET/CT and subsequent radical prostatectomy. All patients were followed for a median of 26 mo, and serum prostate-specific antigen levels were measured every 3 mo to evaluate biochemical failure. One-way analysis of variance, Tukey's multiple comparison test, and Fisher's exact test were performed. RESULTS: All 42 index tumours were detected on [18F]PSMA-1007 PET/CT, whereas only 15 were detected on [18F]FDG PET/CT (62.3% vs. 37.7%, p < 0.0001). A high SUVmax for [18F]PSMA-1007 was observed in tumours with high Gleason scores (GS 6-7 vs. GS 8-10; 12.1 vs. 20.1, p < 0.05). Tumours with [18F]FDG uptake were mostly ductal dominant (acinar-dominant 4/27; ductal-dominant; 11/15, p < 0.001), with lower [18F]PSMA-1007 uptake than tumours without [18F]FDG uptake (SUVmax 16.58 vs. 11.19, p < 0.001). There were 16.6% (7/42) of patients with pStage IV in whom the primary tumours were [18F]FDG positive. Biochemical failure was observed in 14.8% (4/27) of patients with [18F]FDG negative tumours but in 53.3% (8/15) of patients with [18F]FDG positive tumours (p = 0.013). CONCLUSIONS: [18F]PSMA-1007 PET/CT was superior to [18F]FDG PET/CT in detecting primary PCa. In contrast, tumours with [18F]FDG uptake are associated with larger size, a ductal-dominant type, and likely to undergo metastasis at staging and biochemical failure postoperatively.

Phase I/IIa trial of 18F-prostate specific membrane antigen (PSMA) 1007 PET/CT in healthy volunteers and prostate cancer patients.

OBJECTIVE: 18F-PSMA 1007 is a promising PET tracer for prostate cancer. We aimed to examine the safety, biodistribution, radiation dosimetry, and clinical effectiveness in Japanese healthy volunteers and patients with prostate cancer. METHODS: Part A evaluated the pharmacokinetics and exposure doses in three healthy volunteers. Part B evaluated the diagnostic accuracy in patients with untreated preoperative prostate cancer (Cohort 1, n = 7) and patients with biochemical recurrence (Cohort 2, n = 3). All subjects received a single dose of 3.7 MBq/kg 18F-PSMA 1007. Results: 18F-PSMA 1007 was found to be safe and well tolerated in all subjects. No serous AEs or drug-related AEs were identified during the present study. The average blood radioactivity concentration reached a maximum of 47.87 ± 1.05 (percentage of injected dose [%ID]/ml) at 5 min and then decreased to 1.60 ± 0.78 in 6 h. The systemic radioactivity reached a maximum of 211.05 ± 6.77 (%ID$\times$103) at 5 min and decreased to 7.18 ± 3.91 in 6 h. The sensitivity and positive predictive value were 100% and 100% based on both pathologic and imaging confirmation as gold standard. In Cohort 1, 15 primary foci (11.9%) were >5 mm in the largest diameter and identified in 39 of 126 segments (30.1%). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for 60 min uptake time acquisition were 80.0, 96.5, 91.4, 91.2 and 91.3%, respectively. CONCLUSIONS: Our study revealed that 18F-PSMA 1007 was safe, well tolerated and showed high accuracy in the diagnosis of prostate cancer.

Diagnostic value of 18F-PSMA-1007 PET/CT for predicting the pathological grade of prostate cancer.

This study was designed to evaluate the diagnostic efficacy of relevant parameters of 18F-prostate-specific membrane antigen (PSMA)-1007 PET/CT in predicting the pathological grade of primary prostate cancer. Briefly, a prospective analysis was performed on 53 patients diagnosed with prostate cancer by systematic puncture biopsy, followed by 18F-PSMA-1007 PET/CT examination prior to treatment within 10 d. The patients were grouped in accordance with the Gleason grading system revised by the International Association of Urology Pathology (ISUP). They were divided into high-grade group (ISUP 4-5 group) and low-grade group (ISUP 1-3 group). The differences in maximum standardized uptake value (SUVmax), tumor-to-background ratio (TBR), intraprostatic PSMA-derived tumor volume (iPSMA-TV), and intraprostatic total lesion PSMA (iTL-PSMA) between the high- and low-grade group were statistically significant (p < .001). No significant difference was found for mean standardized uptake value (SUVmean) between the high- and low-grade groups (Z = -1.131, p = .258). Besides, binary multivariate logistic regression analysis showed that only iPSMA-TV and iTL-PSMA were independent predictors of the pathological grading, for which the odds ratios were 18.821 [95% confidence interval (CI): 2.040-173.614, p = .010] and 0.758 (95% CI: 0.613-0.938, p = .011), respectively. The area under the ROC of this regression model was 0.983 (95% CI: 0.958-1.00, p < .001). Only iTL-PSMA was a significant parameter for distinguishing ISUP-4 and ISUP-5 groups (Z = -2.043, p = .041). In a nutshell, 18F-PSMA-1007 PET/CT has good application value in predicting the histopathological grade of primary prostate cancer. Three-dimensional volume metabolism parameters iPSMA-TV and iTL-PSMA were found to be independent predictors for pathological grade.

A Critical Analysis of the Robustness of Radiomics to Variations in Segmentation Methods in 18F-PSMA-1007 PET Images of Patients Affected by Prostate Cancer.

BACKGROUND: Radiomics shows promising results in supporting the clinical decision process, and much effort has been put into its standardization, thus leading to the Imaging Biomarker Standardization Initiative (IBSI), that established how radiomics features should be computed. However, radiomics still lacks standardization and many factors, such as segmentation methods, limit study reproducibility and robustness. AIM: We investigated the impact that three different segmentation methods (manual, thresholding and region growing) have on radiomics features extracted from 18F-PSMA-1007 Positron Emission Tomography (PET) images of 78 patients (43 Low Risk, 35 High Risk). Segmentation was repeated for each patient, thus leading to three datasets of segmentations. Then, feature extraction was performed for each dataset, and 1781 features (107 original, 930 Laplacian of Gaussian (LoG) features, 744 wavelet features) were extracted. Feature robustness and reproducibility were assessed through the intra class correlation coefficient (ICC) to measure agreement between the three segmentation methods. To assess the impact that the three methods had on machine learning models, feature selection was performed through a hybrid descriptive-inferential method, and selected features were given as input to three classifiers, K-Nearest Neighbors (KNN), Support Vector Machines (SVM), Linear Discriminant Analysis (LDA), Random Forest (RF), AdaBoost and Neural Networks (NN), whose performance in discriminating between low-risk and high-risk patients have been validated through 30 times repeated five-fold cross validation. CONCLUSIONS: Our study showed that segmentation methods influence radiomics features and that Shape features were the least reproducible (average ICC: 0.27), while GLCM features the most reproducible. Moreover, feature reproducibility changed depending on segmentation type, resulting in 51.18% of LoG features exhibiting excellent reproducibility (range average ICC: 0.68-0.87) and 47.85% of wavelet features exhibiting poor reproducibility that varied between wavelet sub-bands (range average ICC: 0.34-0.80) and resulted in the LLL band showing the highest average ICC (0.80). Finally, model performance showed that region growing led to the highest accuracy (74.49%), improved sensitivity (84.38%) and AUC (79.20%) in contrast with manual segmentation.

Systematic Review and Metanalysis on the Role of Prostate-Specific Membrane Antigen Positron Emission Tomography/Magnetic Resonance Imaging for Intraprostatic Tumour Assessment.

The present systematic review and meta-analysis are focused on the diagnostic accuracy of PSMA PET/MRI in primary prostate cancer assessment. A literature search was conducted on the PubMed database using the terms "PSMA" AND "prostate cancer" or "prostate" AND "PET/MRI" or "PET MRI" or "PET-MRI" or "PET-MR" AND "primary" or "staging." Ten articles were eligible for analysis after applying the exclusion criteria. PET/MRI showed better diagnostic accuracy in detecting primary PCa compared to multiparametric (mp) MRI and PET alone. The pooled sensitivity and specificity of 68Ga-PSMA PET/MRI at the per-patient level were 0.976 (CI: 0.943-0.991) and 0.739 (CI: 0.437-0.912); respectively. PSMA PET/MRI has good sensitivity in detecting primary PCa, especially in patients with PIRADS 3 PCa.

An exploratory study of unexplained concentration of 18F-PSMA-1007 in the bladder for prostate cancer PET/CT imaging.

18F-PSMA-1007 PET/CT imaging is increasingly used for the diagnosis, staging, and efficacy assessment of patients with prostate cancer. Compared with other PSMA tracers, 18F-PSMA-1007 is mainly cleared by the liver and bile and has lower urinary clearance, thus allowing a better assessment of the lesions around the bladder. However, there were some patients who showed an obvious concentration of the 18F-PSMA-1007 in the bladder, which may affect the observation of peripheral lesions, but the mechanism of this change is unknown. The aim of this study was to explore the cause of bladder 18F-PSMA-1007 concentration by assessing the clinical and imaging characteristics of 18F-PSMA-1007 PET/CT scans. A total of 284 patients were included in this retrospective study, and their clinical characteristics such as age, height, weight, Gleason score, metastases, different treatment methods, the level of liver and kidney function, PSA level, and imaging characteristics such as 18F-PSMA-1007 injected activity, the interval between injection to scan, physiological distribution (parotid gland, kidney, liver, spleen, intestine, obturator internus), pathological distribution (prostate lesions, metastases) were collected, and were compared after subgrouping using bladder urine SUVmax. This study showed that the distribution of bladder 18F-PSMA-1007 was not correlated with the above clinical and imaging characteristics, so further studies are needed to find the explanations, and thus to improve the disease assessment of this type of prostate cancer patients.

The potential role of osteoporosis in unspecific [18F]PSMA-1007 bone uptake.

AIM: Unspecific bone uptake is one of the main limitations of PET imaging with some PSMA-targeting radiopharmaceuticals, especially with [18F]PSMA-1007. We explored the potential association between osteoporosis and the occurrence of unspecific [18F]PSMA-1007 bone uptake investigating markers which might correlate with bone mineral density. MATERIALS AND METHODS: We retrospectively analyzed treatment-naïve patients with a confirmed diagnosis of prostate adenocarcinoma who underwent staging [18F]PSMA-1007 positron emission tomography (PET). Qualitative image analysis was performed independently by three experienced nuclear medicine physicians. Patients were divided in two groups according to the presence/absence of unspecific bone uptake. Clinical information, blood count parameters (assessed within 3 months to the PET scan), body mass index (BMI), and bone density as estimated by computed tomography were collected. The Kruskal-Wallis and t-test were used to compare parameters. RESULTS: We analyzed 77 patients: 29 of them (38%) had unspecific bone uptake at [18F]PSMA-1007 PET, most commonly in the pelvic bones (69%) and ribs (62%). We did not find any significant difference in clinical parameters in the two groups. In patients with unspecific bone uptake, white blood cell, and neutrophil counts were significantly higher; in the same group, we observed lower values of BMI and bone density, although not statistically different. CONCLUSIONS: We observed unspecific bone uptake on [18F]PSMA-1007 PET in more than 1/3 of patients. In this exploratory analysis, we found a significant correlation between blood count parameters and unspecific [18F]PSMA-1007 bone uptake. We may speculate that [18F]PSMA-1007 unspecific bone uptake could be associated with osteoporosis. This hypothesis needs to be further investigated in larger populations and exploring more specific markers of osteoporosis.

Application of 18F-PSMA-1007 PET/MR Imaging in Early Biochemical Recurrence of Prostate Cancer: Results of a Prospective Study of 60 Patients with Very Low PSA Levels ≤ 0.5 ng/mL.

The use of 18F-PSMA-1007 and the role of PET/MR in the diagnosis of prostate cancer are not conclusively confirmed. There are reports indicating the potential pros and cons of using 18F-PSMA-1007 as well as the PET/MR technique in prostate cancer recurrence, but they are not yet included in the EAU guidelines. The aim of the study was to assess the effectiveness of 18F-PSMA-1007 PET/MR in detecting BCR lesions at very low PSA levels <0.5 ng/mL. METHODS: Sixty patients with BCR after radical prostatectomy (RP) with PSA ranged 0.1-0.5 ng/mL were enrolled in a prospective study. All patients underwent simultaneous whole-body and pelvic 18F-PSMA-1007 PET/MR. The obtained results were verified by 12-month follow-up. RESULTS: Fifty-three lesions were detected in 45 patients with 75% detection rate. The mean PSA value was 0.31 ng/mL. Of all PSMA-positive foci, 91% were localized in the pelvis, and only 9% of lesions were located in the extrapelvic region. Local recurrences were detected in 29%, PSMA-positive lymph nodes were detected in 64% of patients and bone metastases lesions were detected in 7% of patients. CONCLUSIONS: 18F-PSMA-1007 PET/MR seems to be an excellent diagnostic tool in patients with early BCR with very low PSA levels, especially with dt PSA < 6 months. The synergistic effect of combining 18F-PSMA-1007 and whole-body PET/MR with precise multiparametric assessment of pelvic lesions is of particular benefit in early BCR.

Impact of non-regional lymph node metastases accurately revealed on 18F-PSMA-1007 PET/CT in the clinical management of metastatic hormone-sensitive prostate cancer.

BACKGROUND: Non-regional lymph node (NRLN) metastases has shown increasing importance in the prognosis evaluation and clinical management of primary metastatic hormone-sensitive prostate cancer (mHSPC). Hence, this study aimed to investigate the concordance rates between 18F-PSMA-1007 PET/CT and conventional imaging (CI) in revealing NRLN metastases, and explore the impact of NRLN metastases on the management of primary mHSPC. METHODS: The medical records of 224 patients with primary mHSPC were retrospectively reviewed, including 101 patients (45.1%) only received CI for TNM classification, 24 patients (10.7%) only received 18F-PSMA-1007 PET/CT, and 99 patients (44.2%) received both 18F-PSMA-1007 PET/CT and CI. Among patients who received 18F-PSMA-1007 PET/CT and CI before initial treatment, the concordance rates between 18F-PSMA-1007 PET/CT and CI were analyzed. The high-volume disease was defined as the presence of visceral metastases and/or ≥ 4 bone metastases (≥ 1 beyond the vertebral bodies or the pelvis) based on the findings of 18F-PSMA-1007 PET/CT and/or CI. The primary endpoint was progression-free survival (PFS), and Cox regression analyses were performed to explore independent predictors of PFS. RESULTS: A total of 99 patients (44.2%) received both 18F-PSMA-1007 PET/CT and CI, the concordance rate in revealing NRLN metastases between 18F-PSMA-1007 PET/CT and CI was only 61.62%, and Cohen's kappa coefficient was as low as 0.092. Moreover, 18F-PSMA-1007 PET/CT detected an additional 37 of 94 (39.4%) patients with positive NRLNs who were negative on CI. Cox regression revealed that androgen deprivation therapy (ADT), N1, high-volume, NRLN and visceral metastases were associated with worse PFS (all P < 0.05) in 224 patients. Furthermore, in patients with low-volume disease, the median PFS of patients with NRLN metastases was significantly shorter than that of patients without NRLN metastases (19.5 vs. 27.5 months, P = 0.01), while the difference between patients with low-volume plus NRLN metastases and high-volume disease was not significant (19.5 vs. 16.9 months, P = 0.55). Moreover, early docetaxel chemotherapy significantly prolonged the PFS of these patients compared with ADT alone (20.7 vs. 12.3 months, P = 0.008). CONCLUSION: NRLN metastases could be accurately revealed by 18F-PSMA-1007 PET/CT, which should be considered a high-volume feature, especially concomitant with bone metastases. Furthermore, patients with low-volume plus NRLN metastases may be suitable for more intensive treatment, such as early docetaxel chemotherapy.