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68Ga-labeled prostate specific membrane antigen HBED-CC PET/MRI for staging and evaluating the clinicopathological characteristics in newly diagnosed prostate cancer

Abstract

Objective

The purpose of this study was to investigate the role of 68Ga-labeled prostate specific membrane antigen HBED-CC (68Ga-PSMA-11) PET/MRI in primary staging and to evaluate the relationship between PSMA-derived parameters and clinicopathological characteristics in newly diagnosed prostate cancer (PCa).

Materials and methods

This study reports the findings from 72 patients newly diagnosed with primary PCa, all of whom underwent 68Ga-PSMA-11 PET/MRI scans. Calculated the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 68Ga-PSMA-11 PET/MRI for T, N, M staging, respectively. The maximum standardized uptake value (SUVmax), PSMA-tumor volume (PSMA-TVp), and total lesion-PSMA (TL-PSMAp) of primary lesion, PSMA-TV of total lesions (PSMA-TVt), and TL-PSMA of total lesions (TL-PSMAt) were measured, and Spearman correlation analysis was performed to assess their correlation with baseline prostate-specific antigen (PSA). Non-parametric Mann–Whitney U test was conducted to assess the difference of PSMA-derived parameters among clinicopathological characteristics of PCa. Receiver operating characteristic (ROC) curve was used to evaluate the performance of PSMA-derived parameters in diagnosing the clinicopathological characteristics of PCa.

Results

The overall accuracy of 68Ga-PSMA-11 PET/MRI in detecting T staging of PCa was 80.7%. Diagnostic accuracy for T2a, T2b, T2c, T3a, and T3b were 94.2%, 92.3%, 90.4%, 90.4%, and 94.2%, respectively. Diagnostic accuracy for N and M staging were 96.1% and 97.2% based on patients-level, respectively. There were significant correlation between the SUVmax, PSMA-TVp, TL-PSMAp, PSMA-TVt, TL-PSMAt and baseline PSA values. Significant differences were observed in SUVmax, PSMA-TVp, TL-PSMAp, PSMA-TVt, and TL-PSMAt between T3 and T2 staging. Statistical differences were observed in SUVmax, TL-PSMAp, PSMA-TVt, and TL-PSMAt between Gleason Score (GS) > 7 and GS ≤ 7, as well as positive and negative regional lymph node metastasis. TL-PSMAt show the highest value in assessing clinicopathological characteristics.

Conclusions

68Ga-PSMA-11 PET/MRI can provide accurate TNM staging for PCa, particularly in local staging. TL-PSMAt accurately evaluate overall tumor burden and aids in diagnosing clinicopathological characteristics in mid-to-late-stage patients, outperforming SUVmax.

Background

Prostate cancer (PCa) stands as one of the most prevalent malignant diseases in men worldwide [1,2,3]. PCa often remains asymptomatic in its early staging, with nearly 60% of patients progressing to advanced staging by the time of diagnosis. It manifests as capsular invasion, extra capsular extension (ECE), vascular bundle invasion, regional lymph node involvement, and metastasis to bones and organs, indicating advanced tumor staging, strong invasiveness, and a poor prognosis [4]. Therefore, accurate diagnosis, staging, and assessment of tumor invasiveness are crucial.

Prostate−specific membrane antigen (PSMA) is a type II transmembrane glycoprotein that is highly expressed on the surface of PCa cells, with low expression levels in normal prostate cells [5], and is significantly elevated in intermediate and advanced PCa patients [6, 7]. 68Ga−labeled PSMA HBED-CC (68Ga-PSMA-11) is the most commonly used PET radioactive tracer for PCa [8]. Positron emission tomography/magnetic resonance imaging (PET/MRI) combines the superior soft tissue resolution, multiparametric, and multi−sequence imaging capabilities of MRI with the remarkable sensitivity of PET, enhancing the efficiency of lesion detection and diagnostic accuracy. The clinicopathological characteristics of PCa are closely linked to the treatment strategies, monitoring of biochemical recurrence (BCR), and prognosis assessment [9,10,11,12]. Schmuck et al. first introduced PSMA−tumor volume (PSMA−TV) and total lesion−PSMA (TL−PSMA) to study BCR after radical prostatectomy. The results demonstrated that these parameters were more accurate than the maximum standardized uptake value (SUVmax) in assessing tumor burden in recurrent metastatic lesions [13]. Other studies have identified a correlation between the SUVmax of PSMA in the primary lesion and the clinicopathological characteristics of PCa, such as the prostate−specific antigen (PSA) and Gleason score (GS) [14]. However, few studies have explored the correlation between SUVmax, PSMA−TV, TL−PSMA and local T staging, regional lymph node metastasis, seminal vesicle invasion (SVI), perineural invasion (PNI), and surgical margins.

This study aims to explore the value of 68Ga-PSMA-11 PET/MRI in the TNM staging of newly diagnosed PCa and to investigate the relationship between PSMA−derived parameters and clinicopathological characteristics, with the goal of establishing a reliable imaging basis for the precise diagnosis and treatment of PCa.

Materials and methods

Patients

Patients newly diagnosed with primary PCa who underwent 68Ga-PSMA-11 PET/MRI scans were enrolled in this study between June 2022 and April 2023. This study adhered to the principles of the Helsinki Declaration, and was approved by the Ethics Committee of the First Affiliated Hospital of Anhui Medical University (approval number: PJ2022-05–21).

68Ga-PSMA-11 PET/MRI imaging

The preparation of 68Ga-PSMA-11 was based on references [15,16,17]. All patients received an intravenous injection of 68Ga-PSMA-11 (111–185 MBq, IQR: 138–169 MBq). All patients were encouraged to hydrate after the injection and instructed to empty their bladders before the PET/MRI scan, which was initiated 50–70 min (IQR: 57–64 min) after the tracer injection. Whole-body MRI was conducted according to the PET/MRI scan protocol (Table 1), and all scans were performed using the same PET/MRI (GE Healthcare, USA, SIGNA PET/MR). The PET acquisition times for the head, body, and pelvic regions were 6 min, 22 min, and 20 min, respectively, using TOF as the PET reconstruction algorithm.

Table 1 MRI scan sequence

TNM staging of PCa

The staging of PCa was based on the TNM staging system developed by the American Joint Committee on Cancer (AJCC, 8 th edition). T represents the local extent of the primary tumor, N represents regional lymph nodes metastasis, and M indicates distant metastasis, including non-regional lymph node metastasis, bone metastasis, and metastasis to other organs [18].

Imaging analysis

PET/MRI images were analyzed using the Advantage Workstation version 4.7 (AW4.7, GE Healthcare). Two physicians, both qualified in nuclear medicine and MRI, independently conducted a double-blind review of the images. In cases of disparate opinions, the mutually agreed-upon result was adopted; if an agreement could not be reached, the case was referred to a senior physician for a final diagnosis. MRI was used to precisely determine the location, extent, capsule integrity, and invasion of surrounding tissues in primary PCa lesions, with reference to the Prostate Imaging Reporting and Data System Version 2 (PI-RADS v2) [19]. The gold standard for diagnosing suspected metastasis was pathological analysis. Due to the challenges in obtaining pathological tissue from bone and other distant metastasis, this study employed the best valuable comparator (BVC) clinical diagnostic method [20]. Physiological uptake was observed in the lacrimal glands, salivary glands, liver, kidneys, urethra, and gastrointestinal tract [21].

The SUVmax and mean standardized uptake value (SUVmean) were calculated using the AW4.7. Using the MeMRS Imaging Workstation (Beijing MedEx Technology Co., Ltd.), using 40% SUVmax threshold, the system delineated and calculated the volume of regions of interest (ROI) with values exceeding the 40% SUVmax threshold, which was recorded as PSMA-TV. The product of SUVmean and PSMA-TV was recorded as TL-PSMA. The PSMA-TV and TL-PSMA of the primary lesion were recorded as PSMA-TVp and TL-PSMAp, respectively. The PSMA-TV and TL-PSMA of total lesions within the field of view were recorded as PSMA-TVt and TL-PSMAt, respectively. All PSMA-related parameter ROIs were jointly delineated by two physicians, both qualified in nuclear medicine and MRI diagnostics, with any discrepancies resolved through consensus discussion.

Statistical analysis

All statistical analysis were performed using SPSS 27.0 (IBM, NY, USA) and GraphPad Prism (version 10). Normally distributed data are presented as mean ± standard deviation, while non-normally distributed data are presented as [M (Q1, Q3)]. The Kappa test and Spearman correlation analysis were performed to assess the consistency and correlation, respectively, of T staging between 68Ga-PSMA-11 PET/MRI and pathological findings. The Chi-square test was used to evaluate the accuracy of N and M staging. PSMA-derived parameters were compared across clinicopathological characteristics using the Mann–Whitney U test. Receiver operating characteristic (ROC) curves were generated to assess the diagnostic performance of each PSMA-derived parameters, and to determine the area under curve (AUC). A p-value of < 0.05 was considered statistically significant. A natural logarithm (ln) transformation was applied to part of the skewed data to approximate a normal distribution.

Results

Patients and clinicopathological characteristics

A total of 72 patients newly diagnosed with PCa by histopathology underwent whole-body rapid and pelvic fine 68Ga-PSMA-11 PET/MRI scans. Fifty-two patients underwent surgery after biopsy, with a median interval of 17 days (IQR: 15–23 d). Clinicopathological characteristics, including age, PSA levels, T staging, GS, regional lymph node metastasis, SVI, PNI, and surgical margins, are summarized in Table 2. The remaining 20 patients were diagnosed with distant metastasis and received androgen deprivation therapy.

Table 2 Clinicopathological characteristics of PCa patients

Positivity rate and primary prostate lesion

Among the 72 patients, 68Ga-PSMA-11 PET/MRI results were positive in 70 cases, yielding a positivity rate of 97.2%. 68Ga-PSMA-11 PET/MRI results were positive for T staging in 52 patients. A comparison of T staging between 68Ga-PSMA-11 PET/MRI and histopathology is summarized in Table 3.

Table 3 Comparison of 68Ga-PSMA-11 PET/MRI and pathological T staging in 52 patients with PCa

The accuracy of 68Ga-PSMA-11 PET/MRI in detecting different T stages was 80.7%. The accuracies of T2a, T2b, T2c, T3a, and T3b staging were 94.2%, 92.3%, 90.4%, 90.4%, and 94.2%, respectively (Table 4). The Kappa value for the consistency between PET/MRI and pathological T staging was 0.754 (95% CI 0.609–0.878, P < 0.001). Spearman correlation analysis indicated a significant correlation between 68Ga-PSMA-11 PET/MRI and pathological T staging (r = 0.902, P < 0.001). We present representative 68Ga-PSMA-11 PET/MRI images for different T stages (Fig. 1).

Table 4 Diagnostic performance of 68Ga-PSMA-11 PET/MRI for T staging in 52 patients with PCa (%)
Fig. 1
figure 1

Representative 68Ga-PSMA-11 PET/MRI images for different T stages. a A lesion located in the right peripheral zone, with a pathological stage of T2a and an SUVmax of 3.26. b A lesion located in the left lobe, extending beyond the left half, with a pathological stage of T2b and an SUVmax of 3.12. c A lesion involves both lobes, with a pathological stage of T2c and an SUVmax of 8.09. d A lesion invades bilateral perivascular structures, with a pathological stage of T3a. e A lesion invades the left seminal vesicle, with a pathological stage of T3b and an SUVmax of 3.37

Regional lymph nodes

A total of 20 patients were diagnosed with positive regional lymph node metastasis on preoperative 68Ga-PSMA-11 PET/MRI, which was confirmed by histopathology. Two patients initially tested negative for regional lymph node metastases on preoperative 68Ga-PSMA-11 PET/MRI, but metastasis was confirmed by histopathology.

In patient-based analysis, 68Ga-PSMA-11 PET/MRI demonstrated an accuracy of 96.1%, a sensitivity of 90.9%, a specificity of 100%, a positive predictive value (PPV) of 100%, and a negative predictive value (NPV) of 93.8% for the diagnosis of lymph node metastasis (Table 5). In lesion-based analysis, the accuracy, sensitivity, specificity, PPV, and NPV were 97.4%, 95.2%, 100%, 100%, and 94.6%, respectively. In analyses performed at both the patient and lesion levels, the AUCs for the diagnosis of regional lymph node metastasis using 68Ga-PSMA-11 PET/MRI were 0.955 (95% CI 0.833–1.000) and 0.976 (95% CI 0.938–1.000), respectively. Representative 68Ga-PSMA-11 PET/MRI images of positive regional lymph node metastasis are shown in Fig. 2.

Table 5 Diagnostic performance of 68Ga-PSMA-11 PET/MRI for N and M staging of PCa (%)
Fig. 2
figure 2

Representative 68Ga-PSMA-11 PET/MRI images of positive regional lymph node metastasis. Both (a) and (b) show multiple enlarged pelvic lymph nodes with high PSMA uptake, which were pathologically confirmed as metastases. The SUVmax values for (a) and (b) were 4.62 and 9.28, respectively

Distant metastasis

A total of 18 patients were identified with distant metastasis on 68Ga-PSMA-11 PET/MRI, accounting for 25% of the total cases in this study. The overall number of distant metastatic lesions was 135, distributed as 60 in lymph nodes, 65 in bones, 3 in the liver, and 7 in lungs (Fig. 3). All patients were diagnosed with distant metastasis, with a minimum follow-up period of 6 months. Additionally, two new bone metastatic lesions were identified during clinical follow-up, located in the fifth lumbar vertebra and sternum in two patients, respectively.

Fig. 3
figure 3

Representative 68Ga-PSMA-11 PET/MRI images of positive distant metastasis. a A lesion located in the left lobe of the liver, exhibiting a low T1 signal and high PSMA uptake, with an SUVmax of 7.53. Liver biopsy pathology confirmed compatibility with metastasis from PCa. b A lesion located in the thoracic vertebra and rib, showing a low T1 signal and high PSMA uptake, with an SUVmax of 9.37. After a 6-month clinical follow-up, it was confirmed as bone metastasis

In a patient-based analysis for the diagnosis of distant metastasis using 68Ga-PSMA-11 PET/MRI, the accuracy was 97.2%, the sensitivity was 90.0%, the specificity was 100%, the PPV was 100%, and the NPV was 96.3% (Table 5). The AUC for the diagnosis of distant metastasis using 68Ga-PSMA-11 PET/MRI was 0.950 (95% CI 0.872–1.000).

68Ga-PSMA-11 uptake and clinicopathological characteristics of PCa

Spearman correlation analysis demonstrated significant correlations between SUVmax, PSMA-TVp, TL-PSMAp, PSMA-TVt, TL-PSMAt and baseline PSA values (r = 0.846, 0.620, 0.809, 0.787, 0.883; P < 0.001), with TL-PSMAt showing the strongest correlation. The SUVmax, PSMA-TVp, TL-PSMAp, PSMA-TVt, and TL-PSMAt showed significant differences between the baseline PSA > 20 ng/mL and ≤ 20 ng/mL groups (P < 0.001), as well as between the T3 and T2 staging groups (P < 0.05). The median values of all PSMA-derived parameters in the baseline PSA > 20 ng/mL and T3 staging group exceeded those in baseline PSA ≤ 20 ng/mL and T2 staging groups, respectively. Furthermore, significant differences were observed in SUVmax, TL-PSMAp, PSMA-TVt, and TL-PSMAt between the GS > 7 and GS ≤ 7 groups (P < 0.05), as well as between the positive and negative regional lymph node metastasis groups. The median values of these PSMA-derived parameters were higher in the GS > 7 and positive regional lymph node metastasis groups compared to the GS ≤ 7 and negative regional lymph node metastasis groups, respectively. No significant differences were detected in PSMA-derived parameters between the positive and negative groups for SVI, PNI, and surgical margin status.

The differences in clinicopathological characteristics are presented in Fig. 4. The AUC and ROC curves of PSMA-derived parameters for evaluating clinicopathological characteristics are summarized in Table 6 and Fig. 5, respectively.

Fig. 4
figure 4

Differences in PSMA-derived parameters among various groups based on clinicopathological characteristics

Table 6 Diagnostic performance of PSMA-derived parameters for clinicopathological characteristics of PCa [M (Q1, Q3)]
Fig. 5
figure 5

Diagnostic performance of PSMA-derived parameters for PSA (a), T staging (b), GS (c), and regional lymph node metastasis (d)

Discussion

Early diagnosis and precise staging are crucial for guiding clinical planning, treatment decisions, and prognosis in prostate cancer [22, 23]. Each traditional diagnostic method has its own distinct advantages and limitations [24], while PET/MRI seamlessly integrates the high soft tissue resolution and multimodal imaging capabilities of MRI with the heightened sensitivity of PET [25,26,27]. We aimed to evaluate the diagnostic performance of 68Ga-PSMA-11 PET/MRI for primary staging and to explore the correlation between PSMA-derived parameters and clinicopathological characteristics in newly diagnosed PCa.

Primary prostate lesion

Local staging of prostate cancer relies on the extent of the primary lesion and ECE [20]. In our study of 72 pathologically confirmed prostate cancer patients, 68Ga-PSMA-11 PET/MRI yielded positive results in 70 cases and negative results in 2 cases, achieving a positivity rate of 97.2%. This finding is consistent with previous studies [27] and highlights the superior diagnostic performance of 68Ga-PSMA-11 PET/MRI compared to traditional imaging modalities for detecting PCa [28, 29].

A meta-analysis using mp-MRI reported sensitivities of 57–61% and specificities of 88–96% for detecting ECE, SVI, and T3 staging [30], while 68Ga-PSMA PET/CT showed accuracies of 86% and 71% for SVI and PCa spread, respectively [31]. In contrast, our study demonstrated that 68Ga-PSMA-11 PET/MRI achieves an overall accuracy of 80.7% for local staging, with accuracies for T2a, T2b, T2c, T3a, and T3b staging reaching 94.2%, 92.3%, 90.4%, 90.4%, and 94.2%, respectively (Table 4). Notably, the diagnostic accuracy for T3a and T3b significantly surpasses previous reports. Furthermore, the Kappa test and Spearman correlation analysis revealed excellent strong agreement between 68Ga-PSMA-11 PET/MRI and pathological T staging (Kappa = 0.754, r = 0.902, P < 0.001), underscoring its superior reliability and precision in the local staging of newly diagnosed PCa. These results highlight the potential of 68Ga-PSMA-11 PET/MRI as a transformative tool for improving the accuracy of local T staging.

Regional lymph nodes

Regional lymph node metastasis is a key route of malignant tumor spread [32, 33]. Traditional anatomical imaging, limited to structural details, often yields high false-negative and false-positive rates [34]. While pelvic lymph node dissection with histopathology remains the most accurate method, it carries a higher risk of surgical complications [35]. Studies showed that metastatic lymph nodes specifically uptake PSMA, while unlike non-metastatic nodes, reducing misdiagnosis risks [36].

In our study, 20 patients showed positive lymph nodes on 68Ga-PSMA-11 PET/MRI, confirmed by histopathology, while 2 additional cases were identified post-surgery despite negative PET/MRI findings. Patient- and lesion-based analysis revealed accuracies of 96.1% and 97.4%, respectively, for detecting regional lymph node metastasis, outperforming mp-MRI [24] and matching 68Ga-PSMA-11 PET/CT [37]. The 100% PPV underscores the pivotal role in N staging. Two false-negative cases, attributed to small metastatic lymph nodes (3 mm and 5 mm), fell below the diagnostic threshold. Previous studies suggest smaller nodes may lack PSMA uptake, though rarely [38]. Diagnosing small-volume metastasis remains challenging, underscoring the need for advanced methods. Our results demonstrate the superior diagnostic performance of 68Ga-PSMA-11 PET/MRI, particularly its high PPV and accuracy, solidifying its clinical utility for N staging in PCa.

Distant metastasis

Bone scintigraphy (BS) is recommended for newly diagnosed PCa patients with GS > 7 or PSA > 20 ng/mL [39]. However, assessing tumor burden requires a whole-body imaging, which increases radiation exposure. In contrast, PET/MRI offers superior sensitivity for detecting malignant tumors compared to conventional anatomical imaging and allows comprehensive whole-body evaluation in a single session.

In our study, 18 patients were identified with distant metastasis on 68Ga-PSMA-11 PET/MRI. Notably, BS revealed mild increases in bone metabolism at the fifth lumbar vertebra and sternum in 2 patients, later confirmed as bone metastases during follow-up, despite negative PET/MRI findings. The diagnostic performance of 68Ga-PSMA-11 PET/MRI for distant metastasis demonstrated an accuracy of 97.2%, sensitivity of 90.0%, specificity of 100%, PPV of 100%, NPV of 96.3%, and an AUC of 0.950 (95% CI 0.872–1.000). False-negative cases were likely due to isolated and small-volume metastatic lesions. These results highlight the superior sensitivity and specificity of 68Ga-PSMA-11 PET/MRI for detecting distant metastasis in PCa, underscoring its clinical utility as a comprehensive imaging tool.

PSMA-derived parameters and clinicopathological characteristics of PCa

Patients with advanced PCa are ineligible for surgery and have a poor prognosis, often limited to conservative treatment. Accurate staging, GS, lymph node involvement, SVI, PNI, and surgical margin status remains challenging. Studies have shown that over 50% of high-risk PCa patients experience BCR after initial treatment [40].

Serum PSA levels correlate with PCa aggressiveness and tumor burden [14], with TL-PSMA strongly linked to PSA levels, supporting its role as a BCR biomarker [41]. Our study found that all PSMA-derived parameters correlate with baseline PSA level, with the strongest observed for TL-PSMAt, closely aligning with other study [41]. Significant differences in PSMA-derived parameters were observed between PSA > 20 ng/mL and PSA ≤ 20 ng/mL groups, with TL-PSMAt being the most prominent, suggesting it better reflects tumor invasiveness and systemic burden. T staging is a method used to assess the extent of primary tumor spread [42]. TL-PSMAt outperformed other parameters, demonstrating the most significant differences between T2 and T3 groups. The AUC confirmed TL-PSMAt’s superior diagnostic performance, supporting its use as a supplementary indicator for T staging. GS and regional lymph node metastasis are critical for risk stratification and prognosis [9, 43]. Studies have demonstrated a significant correlation between PSMA uptake values and GS [44, 45]. Our study revealed significant differences in SUVmax, TL-PSMAp, PSMA-TVt, and TL-PSMAt between GS > 7 and GS ≤ 7 groups, as well as between positive and negative regional lymph node metastasis groups, with TL-PSMAt showing the most significant contrast. Higher GS or positive lymph nodes correlated with elevated TL-PSMAt, highlighting its diagnostic value. TL-PSMAt surpassed SUVmax in assessing GS and lymph node metastasis, establishing it as a valuable biomarker for preoperative evaluation.

SVI, PNI, and surgical margins are key PCa staging indicators, reflecting greater invasiveness and poorer prognosis [46,47,48]. Our study found no differences in PSMA-derived parameters between positive and negative SVI, PNI, and surgical margins, consistent with previous findings [49]. However, higher median PSMA-derived parameters in positive SVI and PNI groups suggest a potential influence on their occurrence.

Our study has limitations, including its retrospective design and relatively small sample size. Future research should involve larger prospective studies and further explore TL-PSMA’s impact on prostate cancer treatment decisions.

Conclusions

In conclusion, 68Ga-PSMA-11 PET/MRI can accurately show the primary lesion, ECE, and invasion of nearby tissues, offering precise diagnosis and TNM staging for PCa. TL-PSMAt accurately evaluates overall tumor burden and provides auxiliary diagnostic support for local staging, GS, and preoperative lymph node dissection planning in preoperative or conservatively treated mid-to-late-stage patients.

Availability of data and materials

No datasets were generated or analysed during the current study.

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Acknowledgements

We thank all the staff at the Department of Nuclear Medicine in our hospital for their excellent technical assistance. We would also like to thank the multidisciplinary team in our hospital for their great help with our work.

Funding

This research was supported by the National Natural Science Foundation of China (No. 81801736) and Key project of Anhui Provincial Education Department (KJ2021 A0290).

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Contributions

All authors contributed to the study conception and design. The first draft of the manuscript was written by Xiaoyu Su and Shuangli Yang. Data collation were performed by Xiaoyu Su, Feng Qiao, and Gan Zhu. Date analysis were performed by Xiaoyu Su, Hui Wang, and Tao Wu. Wenjing Yu and Xiao Wang revised the manuscript with constructive ideas. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Wenjing Yu or Xiao Wang.

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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the First Affiliated Hospital of Anhui Medical University (Ethical Code: PJ2022-05-21).

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Informed consent was obtained from all individual participants included in the study.

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The authors declare no competing interests.

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Su, X., Yang, S., Qiao, F. et al. 68Ga-labeled prostate specific membrane antigen HBED-CC PET/MRI for staging and evaluating the clinicopathological characteristics in newly diagnosed prostate cancer. Eur J Med Res 30, 311 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s40001-025-02567-7

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