Research ArticleClinical Investigation

Diagnostic Performance of [18F]AlF-Thretide PET/CT in Patients with Newly Diagnosed Prostate Cancer Using Histopathology as Reference Standard

Jie Zang, Yun Yang, Shaoming Chen, Chao Wang, Shaohao Chen, Shun Hu, Hai Cai, Xiaodong Li, Ning Xu, Xiaoyuan Chen, Jingjing Zhang and Weibing Miao
Journal of Nuclear Medicine July 2024, 65 (7) 1021-1026; DOI: https://doi.org/10.2967/jnumed.123.266940

Abstract

This study aimed to assess the diagnostic value of [18F]AlF-thretide PET/CT in patients with newly diagnosed prostate cancer (PCa). Methods: In total, 49 patients with biopsy-proven PCa were enrolled in this prospective study. All patients underwent [18F]AlF-thretide PET/CT, and the scoring system of the PRIMARY trial was used for PET image analysis. The dosimetry evaluation of [18F]AlF-thretide was performed on 3 patients. Pathologic examination was used as the reference standard to evaluate the location, number, size, and Gleason score of tumors, for comparison with the [18F]AlF-thretide PET/CT results. PSMA expression was evaluated by immunohistochemical staining. Results: All patients tolerated the [18F]AlF-thretide PET/CT well. The total effective dose of [18F]AlF-thretide was 1.16E−02 mSv/MBq. For patient-based analysis of intraprostatic tumors, 46 of 49 (93.9%) patients showed pathologic uptake on [18F]AlF-thretide PET/CT. For lesion-based analysis of intraprostatic tumors, the sensitivity and positive predictive value for [18F]AlF-thretide PET/CT were 58.2% and 90.5%, respectively. Delayed images can detect more lesions than standard images (n = 57 vs. 49, P = 0.005), and the SUVmax and tumor-to-background ratio of the former were higher than those of the latter (SUVmax: 14.5 ± 16.7 vs. 11.4 ± 13.6, P < 0.001; tumor-to-background ratio: 37.1 ± 42.3 vs. 23.1 ± 27.4, P < 0.001). The receiver-operating-characteristic curve analysis showed that the areas under the curve for PRIMARY score–predicted true-positive and false-positive lesions were significantly higher than those for the SUVmax of standard images (P = 0.015) and seemed higher than those for the SUVmax of delayed images (P = 0.257). [18F]AlF-thretide PET/CT showed a higher detection rate than multiparametric MRI for all intraprostatic foci (53.5% vs. 40.8%, P = 0.012) and clinically significant PCa (75.0% vs. 61.4%, P = 0.031). Conclusion: [18F]AlF-thretide PET/CT showed high diagnostic value for patients with primary PCa and can be used as an excellent imaging modality for preoperative evaluation of PCa patients.

Prostate cancer (PCa) is one of the most common malignant neoplasms in men (1). Because of the advancements in various imaging modalities complementing traditional prostate-specific antigen screening, accurate diagnosis in a larger percentage of affected men has been possible in recent years. Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein overexpressed in PCa cells (2). The concept of targeting PSMA for imaging and therapy in PCa has been around since the late 1990s and early 2000s, but it was not until the current decade that PSMA-targeted radiopharmaceuticals entered the field of clinical nuclear medicine, such as the most widely used, [68Ga]Ga-PSMA-11 (3), and its related derivatives including [68Ga]Ga-PSMA-I&T, [18F]F-DCFPyL, [18F]F-PSMA-1007, and [18F]F-rhPSMA-7.3 (4).

For PET imaging,18F-labeled radiotracers have demonstrated several advantages over 68Ga (half-life, 68 min), including the longer half-life (110 min) and larger-scale radiosynthesis, which may allow transportation to satellite nuclear medicine centers and thus benefit more patients (5). In addition, the lower positron emission energy of 18F than of 68Ga (0.65 vs. 1.90 MeV) may also improve the theoretic maximum spatial resolution to obtain higher-quality images (5,6). Al18F labeling is a method that has been viewed as promising because of its simplicity, short reaction time, and potential for kit preparation (7). An Al18F-labeled PSMA ligand (denoted as [18F]AlF-thretide or [18F]AlF-PSMA-BCH) was synthesized using Al18F labeling; this ligand possesses the NOTA structure, strong stability, and the advantages of 18F-labeled radiopharmaceuticals. Previous studies have shown that [18F]AlF-thretide has high stability in vitro and in vivo and can accumulate specifically in PCa with high binding affinity, safety, and selectivity, which may result in high diagnostic efficacy (7).

Here, we aimed to further investigate the diagnostic accuracy and whole-body radiation dosimetry of [18F]AlF-thretide PET/CT in patients with newly diagnosed, treatment-naïve PCa using histopathology as a reference standard.

MATERIALS AND METHODS

This study was approved by the Ethics Committee of the First Affiliated Hospital, Fujian Medical University (approval [2022]023) and registered at ClinicalTrials.gov (NCT05516329). All participants signed a written informed consent form. Participants who met the inclusion criteria (as stated in the supplemental materials, available at http://jnm.snmjournals.org) underwent [18F]AlF-thretide PET/CT.

The patients were observed for any drug-related adverse events, and the vital parameters of the patients were followed up for 1 wk. The methods are detailed in the supplemental data.

Image Analysis

For each eligible patient, 2 nuclear medicine physicians who were unaware of the prostate multiparametric MRI (mpMRI) and pathologic results evaluated the [18F]AlF-thretide images. SUVmax was measured in tumors, and SUVmean was measured in normal organs. The tumor-to-background ratio was defined as the SUVmax of tumors divided by the SUVmean of the gluteus maximus. The scoring system of the PRIMARY trial was used to assess the intraprostatic tumors (8). Briefly, a 5-level PRIMARY score was assigned on the basis of the most clinically significant patterns and SUVmax. Lack of any pattern was given a score of 1; a diffuse transition zone or central zone (not focal), a score of 2; a focal transition zone, a score of 3; a focal peripheral zone, a score of 4; and an SUVmax of at least 12, a score of 5. A PRIMARY score of 3–5 was a high-risk pattern (tumor). For extraprostatic lesions, any focal [18F]AlF-thretide uptake above the surrounding background activity that could not be explained by benign or physiologic tracer uptake was considered a tumor. A consensus of imaging, clinical, and follow-up findings was used to determine the distant metastases, which were not verified by histopathology. Dose estimation based on dynamic PET data was analyzed using Hermes software (Hermes Medical Solutions). Details were as described previously (9).

All mpMR images were interpreted by 2 independent radiologists (with 10 and 15 y of experience in MRI) while masked to [18F]AlF-thretide PET/CT and pathologic data. Any disagreements between readers were resolved by consensus with a third radiologist. The mpMRI component was scored according to Prostate Imaging Reporting and Data System version 2.1 (10). Studies with lesions scored as 3 or above were considered positive.

Histopathology Analysis

A genitourinary pathologist read each section (tissue sections of 4 mm, histologic sections cut at 3 μm, each cross-section divided equally into 4–8 parts) and assessed each lesion for location, area of cancer foci, and International Society of Urological Pathology (ISUP) grade. Then, the histologic samples were digitized using the Motic VM 3.0 digital slice scanning and application system (version 1.0.7.60; Motic China Group Co., Ltd.). The obtained images were arranged and reoriented for comparison between histology and PET imaging. Lesions at the same location on adjacent layers were defined as the same lesion. To define imaging–pathology correspondence on a lesion level, the PET image was rebuilt to a corresponding thickness of 4 mm and a neighboring approach was used (11,12). This approach allowed the location correspondence to involve the immediately adjacent segments to overcome possible interpretation errors from inaccurate registration. Clinically significant PCa was defined as an ISUP grade group of at least 2.

Outcomes

The primary endpoint was diagnostic accuracy, on both a per-patient and a per-lesion basis. The additional primary endpoint was radiation dosimetry evaluation. The secondary endpoint was safety evaluation based on the Common Toxicity Criteria for Adverse Events 5.0.

The methods for patient inclusion and exclusion criteria, radiopharmaceutical, PET imaging procedures, safety evaluation, mpMRI protocol, immunohistochemistry, and statistical analysis are provided in the supplemental materials (13–15).

RESULTS

Patient Characteristics and Safety

From August 2022 to March 2023, 49 patients were enrolled in the study. Among them, 4 patients were rated as having low-risk PCa, 15 patients as having intermediate-risk PCa, and 30 patients as having high-risk PCa. Further patient characteristics are listed in Supplemental Table 1.

All patients tolerated the [18F]AlF-thretide PET/CT well. No significant drug-related side effects were reported during follow-up, and vital parameters remained stable. The results are detailed in the supplemental materials.

Biodistribution and Dosimetry

Three patients underwent dynamic PET scans for dosimetry calculations. The representative maximum-intensity projections and biodistribution data assessed by SUV kinetics are shown in Figure 1. The effective dose of [18F]AlF-thretide was 1.16E−02 mSv/MBq, corresponding to 2.6–3.5 mSv for a target activity of 222–296 MBq. The results for biodistribution and dosimetry are detailed in the supplemental materials, including Supplemental Table 2.

FIGURE 1.
FIGURE 1.

(A) Sequential dynamic maximum-intensity projections of [18F]AlF-thretide PET/CT derived from patient with primary PCa (arrows). (B–D) Time–activity curves based on dynamic PET/CT scans from 3 patients.

Diagnostic Performance of [18F]AlF-Thretide PET/CT Based on Histopathology

As for the interpretation of lesions, 2 observers revealed substantial agreement at the patient level (Fleiss κ = 0.73, P < 0.001) and moderate agreement at the lesion level (Fleiss κ = 0.67, P < 0.001).

The intraprostatic tumors with the highest PRIMARY score in each patient were selected for patient-based analysis. The numbers of patients with PRIMARY scores of 1, 2, 3, 4, and 5 were 2, 1, 2, 22, and 22, respectively. Among the 49 patients, 46 (93.9%) presented with pathologic uptake on [18F]AlF-thretide PET/CT. The SUVmax of the primary tumors on [18F]AlF-thretide PET/CT was 18.7 ± 18.4 at 1 h after injection. There was a weak but significant association between SUVmax and baseline total prostate-specific antigen (r = 0.417, P = 0.004), biopsy Gleason score (r = 0.342, P = 0.031), and risk stratification (r = 0.319, P = 0.027). Similarly, there was also a weak but significant correlation between PRIMARY score and baseline total prostate-specific antigen (r = 0.305, P = 0.037), biopsy Gleason score (r = 0.426, P = 0.006), and risk stratification (r = 0.359, P = 0.011).

Among the 49 patients, 41 underwent radical prostatectomy; however, complete tissue specimens could not be obtained from 10 of these patients because suboptimal preservation damaged the pathologic sections or because the patients underwent surgery at other hospitals. Therefore, only 31 samples underwent full histopathologic analysis. For lesion-based analysis, pathologic examination identified 98 malignant foci, and [18F]AlF-thretide PET/CT identified 63 PET-positive lesions, of which 57 were true-positive and 6 were false-positive (2 lesions were pathologically manifested as prostatitis and 4 lesions as cystic dilatation) (Supplemental Fig. 1). The sensitivity and positive predictive value of intraprostatic tumors for [18F]AlF-thretide PET/CT were 58.2% and 90.5%, respectively. It was noteworthy that the delayed images detected 8 more tumors than did the standard images, and the SUVmax and tumor-to-background ratio of delayed images were higher than those of standard images (n = 57 vs. 49, P = 0.005; SUVmax: 14.5 ± 16.7 vs. 11.4 ± 13.6, P < 0.001; tumor-to-background ratio: 37.1 ± 42.3 vs. 23.1 ± 27.4, P < 0.001) (Fig. 2). Among these PET-positive lesions, 9 lesions had a PRIMARY score of 3, of which 2 (22.2%) were false-positive; 36 lesions had a PRIMARY score of 4, of which 4 (11.1%) were false-positive; and 18 lesions had a PRIMARY score of 5 with no false-positive findings (Figs. 3 and 4). The receiver-operating-characteristic (ROC) curve demonstrated that the area under curve (AUC) for PRIMARY score–predicted true-positive and false-positive lesions was 0.909 (95% CI, 0.806–1.011), which was significantly higher than that for the SUVmax of standard images (AUC, 0.712; 95% CI, 0.590–0.833; P = 0.015) and seemed higher than that for the SUVmax of delayed images (AUC, 0.829; 95% CI, 0.729–0.930; P = 0.257) (Fig. 4). The optimal diagnostic cutoff for the PRIMARY score according to ROC analysis was 3.5. When the PRIMARY score was greater than 3.5, sensitivity and specificity were 86.5% and 83.8%, respectively. Using an SUVmax of 4.8 for standard images as a cutoff, sensitivity and specificity were 63.5% and 91.7%, respectively. Similarly, with an SUVmax of 5.0 for delayed images as a cutoff, the values were 69.2% and 91.7%, respectively.

FIGURE 2.
FIGURE 2.

A 63-y-old man with biopsy-proven PCa with prostate-specific antigen level of 12.60 ng/mL at time of [18F]AlF-thretide PET/CT. (B) Standard images revealed distinct uptake in right peripheral zone (red arrows) (C) Delayed images demonstrated another focus of activity in left peripheral zone (blue arrows). (D) Hematoxylin–eosin staining confirmed bilateral tumors (right peripheral zone, ISUP grade of 2; left peripheral zone, ISUP grade of 1) (top), and immunohistochemical results showed strong PSMA expression (bottom).

FIGURE 3.
FIGURE 3.

(A) [18F]AlF-thretide PET/CT showed multifocal true-positive tumors (PRIMARY scores of 3, 4, and 4, indicated by red, green, and blue arrows, respectively). There was high imaging–pathology correspondence. (B) [18F]AlF-thretide PET/CT revealed true-positive tumors (PRIMARY score of 5, red arrow) and false-negative tumor (PRIMARY score of 1, black arrow).

FIGURE 4.
FIGURE 4.

(A) Diagnostic sensitivity of [18F]AlF-thretide PET/CT improved with increasing PRIMARY score. (B) ROC curves for PRIMARY score and for SUVmax of standard and delayed images.

In total, 98 lesions were detected by pathology, and 41 lesions (41.8%) were missed by PET/CT. The pathologic area of true-positive lesions was significantly larger than that of false-negative lesions (139.7 ± 170.6 mm2 vs. 3.4 ± 4.1 mm2, P < 0.001). The ROC curve analysis showed that the AUC for the pathologic area was 0.957 (95% CI, 0.917–0.996) in distinguishing between true-positive and false-negative lesions. The optimal diagnostic cutoff for area according to the ROC analysis was 9.15 mm2, and the resulting sensitivity and specificity were 87.0%, and 95.1%, respectively. Among 41 lesions missed by PET/CT, 28 (68.3%) had an ISUP grade group of 1. The AUC for the ISUP grade group–predicted true-positive and false-negative lesions was 0.774 (95% CI, 0.673–0.875). Using the ISUP grade group of 1.5 as a cutoff, sensitivity and specificity were 80.4% and 73.2%, respectively.

Detailed data on diagnosis of lymph node and other metastases for [18F]AlF-thretide PET/CT based on histopathology and comprehensive imaging analysis are in the supplemental materials, including Supplemental Table 3.

Diagnostic Performance of [18F]AlF-Thretide PET/CT Versus mpMRI

All patients underwent mpMRI examination: 37 patients at our hospital and the other 12 patients at an outside institution. Finally, 24 individuals with full mpMRI, PET/CT, and pathology results were included for comparison and analysis.

For patient-based analysis, the detection rate for intraprostatic tumor was 100% (24/24) and 95.8% (23/24) for [18F]AlF-thretide PET/CT and mpMRI, respectively. For lesion-based analysis, pathologic examination identified 71 malignant foci. [18F]AlF-thretide PET/CT had a higher detection rate than mpMRI (53.5% [38/71] vs. 40.8% [29/71], P = 0.012); Specifically, [18F]AlF-thretide PET/CT identified 10 lesions missed by mpMRI, whereas mpMRI identified 1 lesion missed by [18F]AlF-thretide PET/CT (Supplemental Fig. 2). In addition, 44 of 71 lesions (62.0%) were graded as clinically significant PCa. The detection rate for clinically significant PCa was 75.0% (33/44) and 61.4% (27/44) for [18F]AlF-thretide PET/CT and mpMRI (P = 0.031), respectively.

Detailed data on diagnosis of lymph node and bone metastases for [18F]AlF-thretide PET/CT compared with mpMRI are in the supplemental materials.

Immunohistochemistry of PSMA Expression

Thirty-eight surgical specimens of intraprostatic tumors were analyzed with immunohistochemistry. PSMA expression was negative in 2 (5.2%), mild in 3 (7.9%), moderate in 9 (23.7%), and strong in 24 (63.2%). The Spearman correlation coefficient revealed a moderate correlation between SUVmax and intensity of staining (r = 0.449, P = 0.005), percentage of positive cells (r = 0.490, P = 0.002), and immunoreactive score (r = 0.540, P < 0.001). Besides, we also found that prostatitis and cystic dilatation had weak to strong PSMA expression, which was consistent with the [18F]AlF-thretide PET images.

DISCUSSION

In this single-center, prospective study, we confirmed that [18F]AlF-thretide PET/CT has high accuracy in the detection of PCa, along with satisfactory safety and radiation dosimetry, indicating that [18F]AlF-thretide is a promising radiopharmaceutical and worthy of further research.

In line with previous research (7), the biodistribution of [18F]AlF-thretide from 0 to 2.5 h after administration revealed rapid and high tumor uptake, long tumor retention, and urinary excretion, which were similar to the tracers [68Ga]Ga-PSMA-11 and [18F]F-DCFPyL (16,17). Furthermore, the effective dose of [18F]AlF-thretide (1.16E−02 mSv/MBq) was close to previous findings from 11 PCa patients (7). In addition, no clinically significant drug-related adverse events were observed in any of the 49 patients during follow-up, indicating its safety and tolerability.

[18F]AlF-thretide PET/CT showed high diagnostic accuracy in patients with primary PCa. In a per-patient analysis, the total detection rate of intraprostatic tumors for [18F]AlF-thretide PET/CT was 93.9%, which was slightly higher than the reported detectability of [68Ga]Ga-PSMA-11, [68Ga]Ga-PSMA-I&T, and [18F]F-DCFPyL PET/CT (18–20). In a per-lesion analysis, [18F]AlF-thretide PET/CT also revealed high diagnostic efficiency, with a sensitivity of 58.2% and a positive predictive value of 90.5%, which were also higher than the reported detection rate of [18F]F-PSMA-1007 PET/CT (21). In our study, we used a 5-level PRIMARY score to optimize the diagnosis of intraprostatic tumor for [18F]AlF-thretide PET/CT. Through comparative analysis, we found that the PRIMARY score was more accurate than visual SUV analysis, and the detection sensitivity of [18F]AlF-thretide PET/CT also improved with increasing PRIMARY score. Several prospective studies have previously tried to establish the best SUVmax cutoff to improve the reliability and reproducibility of PSMA-ligand PET/CT (22,23); however, this is a method that may lack general applicability in clinical practice because of the strong influence of unharmonized PET cameras, differing reconstruction algorithms, and especially variable PSMA ligands on the semiquantitative calculation of SUV (8). The PRIMARY score incorporating intraprostatic pattern and intensity on PSMA PET/CT may achieve high interreader agreement and has the potential to be applied as a standardized PSMA PET/CT reporting method. However, it was noteworthy that CT scans with poor anatomic resolution for the prostate may have difficulty distinguishing the central zone/transition zone from the peripheral zone because of prostatic hyperplasia. As a result, some lesions with a true PRIMARY score of 2–3 may be incorrectly classified as having a score of 4, which may reduce the specificity of the PRIMARY score while guaranteeing the sensitivity (8). In the future, clinical trials based on PSMA PET/MRI may be necessary for further analysis of accuracy for the PRIMARY score.

Additionally, delayed [18F]AlF-thretide PET images showed better diagnostic performance than standard images, although extra findings did not alter the overall staging of the patients. Hence, we suggest that 1 h may be the optimal interval between [18F]AlF-thretide injection and PET imaging—similar to most other PSMA-targeting radiotracers (4). Of course, a delayed scan at 2.5–3 h after injection also remains necessary for improved contrast and visualization of any indeterminate findings observed on standard images.

On the basis of histopathology analysis, we found that false-negative lesions were smaller and had lower ISUP scores than true-positive lesions. The area of true-positive tumors on [18F]AlF-thretide PET was much larger than that of false-negative lesions, and the latter showed an average diameter of approximately 3 mm, which was acceptable, considering that most existing PET/CT scanners have an average transverse and axial spatial resolution of 3–5 mm (24,25). With the advancement of PET scanners and reconstruction algorithms, the ability of [18F]AlF-thretide PET to detect small lesions may improve further in the future. In addition, some studies have illustrated that PSMA PET/CT had lower diagnostic efficacy in low- and intermediate-risk PCa than in high-risk PCa (26,27). In our study, among the false-negative tumors, 68.3% of lesions had an ISUP grade group of 1, which is generally consistent with the findings of previous studies.

Multiparameter prostate MRI plays an important role in the detection and treatment of primary PCa. Johnson et al. (28) showed that mpMRI detected 45% of all lesions and 65% of clinically significant lesions. There is still over a 50% and 30% chance of missing all PCa and clinically significant PCa, respectively, in men with multifocal disease. Therefore, additional methods are needed to better identify PCa foci. In our study, we found that [18F]AlF-thretide PET/CT had a higher detection rate than mpMRI for all intraprostatic foci and clinically significant PCa. However, because of the limited cohort, there was no statistical difference between the 2 imaging modalities in detecting lymph node and bone metastasis.

Furthermore, the immunohistochemistry results confirmed that PSMA was overexpressed in most prostatic tumors. There was a significant positive correlation between the SUV of [18F]AlF-thretide PET/CT and the expression levels of PSMA, which constituted the molecular prerequisite for PSMA imaging. Similar to some previous studies (3,29), we also found that some benign prostatic lesions had different levels of PSMA expression, which resulted in false-positive findings on the [18F]AlF-thretide PET images. This should be kept in mind as a potential pitfall.

As for the detection of lymph node, bone, and visceral metastases, [18F]AlF-thretide PET/CT showed excellent diagnostic performance, better perhaps than some other compounds in previously reported studies (20,30–32). However, the small sample size of nodal disease in this study may result in bias; further validation of larger cohorts is still needed in the future.

Our study had several limitations, including the relatively small sample size, the lack of pathologic confirmation of suspected bone metastases, and the lack of confirmation of PSMA expression for lymph node metastases.

CONCLUSION

In this prospective study, [18F]AlF-thretide PET/CT demonstrated excellent tumor detection efficacy with favorable tolerability in patients with primary PCa. In particular, the detectability of [18F]AlF-thretide PET/CT for intraprostatic tumors was significantly superior to mpMRI. Our findings suggest that [18F]AlF-thretide may serve as an improved alternative to currently routinely used PSMA-targeted radiopharmaceuticals. Further investigations on larger cohorts are warranted.

DISCLOSURE

This work was supported by the Fujian Provincial Health Technology Project (2021GGA026), the National Natural Science Foundation of China (82202200), the Natural Science Foundation of Fujian Province (2022J05139), Joint Funds for the Innovation of Science and Technology of Fujian Province (2021Y9134), the National University of Singapore (NUHSRO/2021/097/Startup/13; NUHSRO/2020/133/Startup/08; NUHSRO/2023/008/NUSMed/TCE/LOA), an NMRC CS-IRG NIG grant (MOH-001254), the Singapore Ministry of Education (FY2022) a Tier 1 grant (NUHSRO/2022/093/T1/Seed-Sep/06), and the NUS School of Medicine Nanomedicine Translational Research Programme (NUHSRO/2021/034/TRP/09/Nanomedicine). No other potential conflict of interest relevant to this article was reported.

KEY POINTS

QUESTION: What is the diagnostic efficiency of [18F]AlF-thretide PET/CT in patients with newly diagnosed, treatment-naïve PCa using histopathology as a reference standard?

PERTINENT FINDINGS: This histopathologically validated, prospective study showed that 46 of 49 (93.9%) patients showed pathologic [18F]AlF-thretide uptake for intraprostatic tumors based on per-patient analysis. For lesion-based analysis, the sensitivity and positive predictive value for [18F]AlF-thretide PET/CT were 58.2% and 90.5%, respectively.

IMPLICATIONS FOR PATIENT CARE: [18F]AlF-thretide PET/CT showed high diagnostic efficiency for patients with newly diagnosed PCa and can be used as an alternative PSMA imaging agent in the detection of PCa.

Footnotes

  • ↵* Contributed equally to this work.

  • ↵† Contributed equally to this work.

  • Published online May 9, 2024.

REFERENCES

  1. 1.↵
    1. Siegel RL,
    2. Miller KD,
    3. Fuchs HE,
    4. Jemal A
    . Cancer statistics, 2021. CA Cancer J Clin. 2021;71:7–33.
    OpenUrlCrossRefPubMed
  2. 2.↵
    1. Leek J,
    2. Lench N,
    3. Maraj B,
    4. et al
    . Prostate-specific membrane antigen: evidence for the existence of a second related human gene. Br J Cancer. 1995;72:583–588.
    OpenUrlCrossRefPubMed
  3. 3.↵
    1. Kuten J,
    2. Fahoum I,
    3. Savin Z,
    4. et al
    . Head-to-head comparison of 68Ga-PSMA-11 with 18F-PSMA-1007 PET/CT in staging prostate cancer using histopathology and immunohistochemical analysis as a reference standard. J Nucl Med. 2020;61:527–532.
    OpenUrlAbstract/FREE Full Text
  4. 4.↵
    1. Fendler WP,
    2. Eiber M,
    3. Beheshti M,
    4. et al
    . PSMA PET/CT: joint EANM procedure guideline/SNMMI procedure standard for prostate cancer imaging 2.0. Eur J Nucl Med Mol Imaging. 2023;50:1466–1486.
    OpenUrl
  5. 5.↵
    1. Kesch C,
    2. Vinsensia M,
    3. Radtke JP,
    4. et al
    . Intraindividual comparison of 18F-PSMA-1007 PET/CT, multiparametric MRI, and radical prostatectomy specimens in patients with primary prostate cancer: a retrospective, proof-of-concept study. J Nucl Med. 2017;58:1805–1810.
    OpenUrlAbstract/FREE Full Text
  6. 6.↵
    1. Grünig H,
    2. Maurer A,
    3. Thali Y,
    4. et al
    . Focal unspecific bone uptake on [18F]-PSMA-1007 PET: a multicenter retrospective evaluation of the distribution, frequency, and quantitative parameters of a potential pitfall in prostate cancer imaging. Eur J Nucl Med Mol Imaging. 2021;48:4483–4494.
    OpenUrl
  7. 7.↵
    1. Liu T,
    2. Liu C,
    3. Xu X,
    4. et al
    . Preclinical evaluation and pilot clinical study of Al18F-PSMA-BCH for prostate cancer PET imaging. J Nucl Med. 2019;60:1284–1292.
    OpenUrlAbstract/FREE Full Text
  8. 8.↵
    1. Emmett L,
    2. Papa N,
    3. Buteau J,
    4. et al
    . The PRIMARY score: using intraprostatic 68Ga-PSMA PET/CT patterns to optimize prostate cancer diagnosis. J Nucl Med. 2022;63:1644–1650.
    OpenUrlAbstract/FREE Full Text
  9. 9.↵
    1. Zang J,
    2. Wen X,
    3. Lin R,
    4. et al
    . Synthesis, preclinical evaluation and radiation dosimetry of a dual targeting PET tracer [68Ga]Ga-FAPI-RGD. Theranostics. 2022;12:7180–7190.
    OpenUrl
  10. 10.↵
    1. Turkbey B,
    2. Rosenkrantz AB,
    3. Haider MA,
    4. et al
    . Prostate Imaging Reporting and Data System version 2.1: 2019 Update of Prostate Imaging Reporting and Data System version 2. Eur Urol. 2019;76:340–351.
    OpenUrlCrossRefPubMed
  11. 11.↵
    1. Turkbey B,
    2. Pinto PA,
    3. Mani H,
    4. et al
    . Prostate cancer: value of multiparametric MR imaging at 3 T for detection—histopathologic correlation. Radiology. 2010;255:89–99.
    OpenUrlCrossRefPubMed
  12. 12.↵
    1. Sonni I,
    2. Felker ER,
    3. Lenis AT,
    4. et al
    . Head-to-head comparison of 68Ga-PSMA-11 PET/CT and mpMRI with a histopathology gold standard in the detection, intraprostatic localization, and determination of local extension of primary prostate cancer: results from a prospective single-center imaging trial. J Nucl Med. 2022;63:847–854.
    OpenUrlAbstract/FREE Full Text
  13. 13.↵
    1. Mohler JL,
    2. Antonarakis ES,
    3. Armstrong AJ,
    4. et al
    . Prostate cancer, version 2.2019, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2019;17:479–505.
    OpenUrlCrossRefPubMed
  14. 14.
    1. Hale CA,
    2. Fleiss JL
    . Interval estimation under two study designs for kappa with binary classifications. Biometrics. 1993;49:523–534.
    OpenUrlCrossRefPubMed
  15. 15.↵
    1. Landis JR,
    2. Koch GG
    . The measurement of observer agreement for categorical data. Biometrics. 1977;33:159–174.
    OpenUrlCrossRefPubMed
  16. 16.↵
    1. Prasad V,
    2. Steffen IG,
    3. Diederichs G,
    4. Makowski MR,
    5. Wust P,
    6. Brenner W
    . Biodistribution of [68Ga]PSMA-HBED-CC in patients with prostate cancer: characterization of uptake in normal organs and tumour lesions. Mol Imaging Biol. 2016;18:428–436.
    OpenUrl
  17. 17.↵
    1. Szabo Z,
    2. Mena E,
    3. Rowe SP,
    4. et al
    . Initial evaluation of [18F]DCFPyL for prostate-specific membrane antigen (PSMA)-targeted PET imaging of prostate cancer. Mol Imaging Biol. 2015;17:565–574.
    OpenUrlCrossRefPubMed
  18. 18.↵
    1. Hope TA,
    2. Goodman JZ,
    3. Allen IE,
    4. Calais J,
    5. Fendler WP,
    6. Carroll PR
    . Metaanalysis of 68Ga-PSMA-11 PET accuracy for the detection of prostate cancer validated by histopathology. J Nucl Med. 2019;60:786–793.
    OpenUrlAbstract/FREE Full Text
  19. 19.
    1. Pan KH,
    2. Wang JF,
    3. Wang CY,
    4. et al
    . Evaluation of 18F-DCFPyL PSMA PET/CT for prostate cancer: a meta-analysis. Front Oncol. 2021;10:597422.
    OpenUrl
  20. 20.↵
    1. Cytawa W,
    2. Seitz AK,
    3. Kircher S,
    4. et al
    . 68Ga-PSMA I&T PET/CT for primary staging of prostate cancer. Eur J Nucl Med Mol Imaging. 2020;47:168–177.
    OpenUrl
  21. 21.↵
    1. Tragardh E,
    2. Simoulis A,
    3. Bjartell A,
    4. Jogi J
    . Tumor detection of 18F-PSMA-1007 in the prostate gland in patients with prostate cancer using prostatectomy specimens as reference method. J Nucl Med. 2021;62:1735–1740.
    OpenUrlAbstract/FREE Full Text
  22. 22.↵
    1. Fendler WP,
    2. Schmidt DF,
    3. Wenter V,
    4. et al
    . 68Ga-PSMA PET/CT detects the location and extent of primary prostate cancer. J Nucl Med. 2016;57:1720–1725.
    OpenUrlAbstract/FREE Full Text
  23. 23.↵
    1. Wang G,
    2. Li L,
    3. Zhu M,
    4. et al
    . A prospective head-to-head comparison of [68Ga]Ga-P16-093 and [68Ga]Ga-PSMA-11 PET/CT in patients with primary prostate cancer. Eur J Nucl Med Mol Imaging. 2023;50:3126–3136.
    OpenUrl
  24. 24.↵
    1. van Sluis J,
    2. de Jong J,
    3. Schaar J,
    4. et al
    . Performance characteristics of the digital Biograph Vision PET/CT system. J Nucl Med. 2019;60:1031–1036.
    OpenUrlAbstract/FREE Full Text
  25. 25.↵
    1. Sánchez-Crespo A,
    2. Andreo P,
    3. Larsson SA
    . Positron flight in human tissues and its influence on PET image spatial resolution. Eur J Nucl Med Mol Imaging. 2004;31:44–51.
    OpenUrlCrossRefPubMed
  26. 26.↵
    1. Uprimny C,
    2. Kroiss AS,
    3. Decristoforo C,
    4. et al
    . 68Ga-PSMA-11 PET/CT in primary staging of prostate cancer: PSA and Gleason score predict the intensity of tracer accumulation in the primary tumour. Eur J Nucl Med Mol Imaging. 2017;44:941–949.
    OpenUrlCrossRefPubMed
  27. 27.↵
    1. Zhou C,
    2. Tang Y,
    3. Deng Z,
    4. et al
    . Comparison of 68Ga-PSMA PET/CT and multiparametric MRI for the detection of low- and intermediate-risk prostate cancer. EJNMMI Res. 2022;12:10.
    OpenUrl
  28. 28.↵
    1. Johnson DC,
    2. Raman SS,
    3. Mirak SA,
    4. et al
    . Detection of individual prostate cancer foci via multiparametric magnetic resonance imaging. Eur Urol. 2019;75:712–720.
    OpenUrlPubMed
  29. 29.↵
    1. Rahbar K,
    2. Weckesser M,
    3. Huss S,
    4. et al
    . Correlation of intraprostatic tumor extent with 68Ga-PSMA distribution in patients with prostate cancer. J Nucl Med. 2016;57:563–567.
    OpenUrlAbstract/FREE Full Text
  30. 30.↵
    1. Klingenberg S,
    2. Jochumsen MR,
    3. Ulhoi BP,
    4. et al
    . 68Ga-PSMA PET/CT for primary lymph node and distant metastasis NM staging of high-risk prostate cancer. J Nucl Med. 2021;62:214–220.
    OpenUrlAbstract/FREE Full Text
  31. 31.
    1. Jansen BHE,
    2. Bodar YJL,
    3. Zwezerijnen GJC,
    4. et al
    . Pelvic lymph-node staging with 18F-DCFPyL PET/CT prior to extended pelvic lymph-node dissection in primary prostate cancer: the SALT trial. Eur J Nucl Med Mol Imaging. 2021;48:509–520.
    OpenUrl
  32. 32.↵
    1. Pienta KJ,
    2. Gorin MA,
    3. Rowe SP,
    4. et al
    . A phase 2/3 prospective multicenter study of the diagnostic accuracy of prostate specific membrane antigen PET/CT with 18F-DCFPyL in prostate cancer patients (OSPREY). J Urol. 2021;206:52–61.
    OpenUrlPubMed
  • Received for publication October 24, 2023.
  • Accepted for publication March 25, 2024.
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