Accuracy of standard clinical 3T prostate MRI for pelvic lymph node staging: Comparison to 68Ga-PSMA PET-CT.

The aim was to assess the performance of prostate 3T MRI for pelvic lymph node (LN) staging in prostate cancer (PCa), in comparison to 68Gallium-prostate specific membrane antigen PET-CT (68Ga-PSMA PET-CT) as reference standard for LN detection. 130 patients with PCa underwent non-contrast-enhanced multiparametric prostate 3T MRI and 68Ga-PSMA-PET-CT within 180 days at our institution. Overall, 187 LN metastases (n = 43 patients) detected by 68Ga-PSMA-PET-CT were characterized by calculating maximum standardized uptake value (SUVmax), area, diameter and anatomical location including iliac, obturator, presacral and inguinal region. MRI achieved an overall sensitivity, specificity, positive and negative predictive value of 81.6% (CI 71.1-88.9%), 98.6% (CI 97.6-99.2%), 73.5% (CI 52.1-87.6%) and 99.5% (CI 98.8-99.8%), respectively. On a region-based analysis, detection rates differed non-significantly (ps > 0.12) in the anatomical regions. On a size-dependent analysis, detection of LN > 10 mm did not differ significantly (ps > 0.09) from LN ≤ 10 mm. In comparison to single T1 sequence evaluation, additional use of the T2 weighted sequences did not improve the overall performance significantly (p > 0.05). 3T prostate MRI represented an accurate tool for the detection of LN compared to 68Ga-PSMA-PET-CT. Especially for LN metastases smaller than 10 mm, MRI was less accurate compared to 68Ga-PSMA-PET-CT.

68Ga-PSMA-PET/CT for the evaluation of liver metastases in patients with prostate cancer.

BACKGROUND: The purpose of this study was to evaluate the imaging properties of hepatic metastases in 68Ga-PSMA positron emission tomography (PET) in patients with prostate cancer (PC). METHODS: 68Ga-PSMA-PET/CT scans of PC patients available in our database were evaluated retrospectively for liver metastases. Metastases were identified using 68Ga-PSMA-PET, CT, MRI and follow-up scans. Different parameters including, maximum standardized uptake values (SUVmax) of the healthy liver and liver metastases were assessed by two- and three-dimensional regions of interest (2D/3D ROI). RESULTS: One hundred three liver metastases in 18 of 739 PC patients were identified. In total, 80 PSMA-positive (77.7%) and 23 PSMA-negative (22.3%) metastases were identified. The mean SUVmax of PSMA-positive liver metastases was significantly higher than that of the normal liver tissue in both 2D and 3D ROI (p ≤ 0.05). The mean SUVmax of PSMA-positive metastases was 9.84 ± 4.94 in 2D ROI and 10.27 ± 5.28 in 3D ROI; the mean SUVmax of PSMA-negative metastases was 3.25 ± 1.81 in 2D ROI and 3.40 ± 1.78 in 3D ROI, and significantly lower than that of the normal liver tissue (p ≤ 0.05). A significant (p ≤ 0.05) correlation between SUVmax in PSMA-positive liver metastases and both size (ρSpearman = 0.57) of metastases and PSA serum level (ρSpearman = 0.60) was found. CONCLUSIONS: In 68Ga-PSMA-PET, the majority of liver metastases highly overexpress PSMA and is therefore directly detectable. For the analysis of PET images, it has to be taken into account that also a significant portion of metastases can only be detected indirectly, as these metastases are PSMA-negative.

68 Ga-PSMA-PET/CT for the evaluation of pulmonary metastases and opacities in patients with prostate cancer.

BACKGROUND: The purpose of this study was to investigate the imaging properties of pulmonary metastases and benign opacities in 68Ga-PSMA positron emission tomography (PET) in patients with prostate cancer (PC). METHODS: 68Ga-PSMA-PET/CT scans of 739 PC patients available in our database were evaluated retrospectively for lung metastases and non-solid focal pulmonary opacities. Maximum standardized uptake values (SUVmax) were assessed by two- and three-dimensional regions of interest (2D/3D ROI). Additionally CT features of the lesions, such as location, morphology and size were identified. RESULTS: Ninety-one pulmonary metastases and fourteen opacities were identified in 34 PC patients. In total, 66 PSMA-positive (72.5%) and 25 PSMA-negative (27.5%) metastases were identified. The mean SUVmax of pulmonary opacities was 2.2±0.7 in 2D ROI and 2.4±0.8 in 3D ROI. The mean SUVmax of PSMA-positive pulmonary metastases was 4.5±2.7 in 2D ROI and in 4.7±2.9 in 3D ROI; this was significantly higher than the SUVmax of pulmonary opacities in both 2D and 3D ROI (p<0.001). The mean SUVmax of PSMA-negative metastases was 1.0±0.5 in 2D ROI and 1.0±0.4 in 3D ROI, and significantly lower than that of the pulmonary opacities (p<0.001). A significant (p<0.05) weak linear correlation between size and 3D SUVmax in lung metastases (ρSpearman=0.207) was found. CONCLUSION: Based on the SUVmax in 68Ga-PSMA-PET alone, it was not possible to differentiate between pulmonary metastases and pulmonary opacities. The majority of lung metastases highly overexpressed PSMA, while a relevant number of metastases were PSMA-negative. Pulmonary opacities demonstrated a moderate tracer uptake, significantly lower than PSMA-positive lung metastases, yet significantly higher than PSMA-negative metastases.

Comparison of hybrid 68Ga-PSMA-PET/CT and 99mTc-DPD-SPECT/CT for the detection of bone metastases in prostate cancer patients: Additional value of morphologic information from low dose CT.

PURPOSE: This study compared 68Gallium-prostate-specific-membrane-antigen based Positron-emission-tomography (68Ga-PSMA-PET) and 99metastabletechnetium-3,3-diphospho-1,2-propanedicarbonacid (99mTc-DPD-SPECT) in performing skeletal staging in prostate cancer (PC) patients and evaluated the additional value of the information from low-dose-computed tomography (CT). MATERIALS AND METHODS: In this retrospective study, 54 patients who received 68Ga-PSMA-PET/CT and 99mTc-DPD-SPECT/CT within 80 days were extracted from our database. Osseous lesions were classified as benign, malignant or equivocal. Lesion, region and patient based analysis was performed with and without CT fusion. The reference standard was generated by defining a best valuable comparator (BVC) containing information from all available data. RESULTS: In the patient based analysis, accuracies measured as "area-under-the-curve" (AUC) for 68Ga-PSMA-PET, 99mTc-SPECT, 68Ga-PSMA-PET/CT and 99mTc-SPECT/CT were 0.97-0.96, 0.86-0.83, 1.00 and 0.83, respectively (p<0.05) (ranges = optimistic vs. pessimistic view). Region based analysis resulted in the following sensitivities and specificities: 91.8-97.7%, 100-99.5% (PET); 61.2-70.6%, 99.8-98.3% (SPECT); 97.7%, 100% (PET/CT), 69.4% and 98.3% (SPECT/CT) (p<0.05). The amount of correct classifications of equivocal lesions by CT was significantly higher in PET (100%) compared to SPECT (52.4%) (p<0.05). CONCLUSION: 68Ga-PSMA-PET outperforms 99mTc-DPD-SPECT in detecting bone metastases in PC patients. Additional information from low-dose-CT resulted in a significant reduction in equivocal lesions in both modalities, however 68Ga-PSMA-PET benefited most. KEY POINTS: • Ga-PSMA-PET outperforms 99m Tc-DPD-SPECT in skeletal staging in prostate cancer patients • Proportion of equivocal decisions was significantly reduced by CT-fusion in both modalities • Ga-PSMA-PET benefits more from CT information, compared to 99m Tc-DPD-SPECT.

Immunohistochemical Validation of PSMA Expression Measured by 68Ga-PSMA PET/CT in Primary Prostate Cancer.

68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA) PET/CT has a proven role in staging and restaging of prostate cancer (PCA). The aims of this study were to evaluate the association of intraprostatic 68Ga-PSMA PET/CT findings and PSMA expression in immunohistochemical staining and generate a cutoff value for differentiation between normal prostate (PN) and PCA. Methods: The data of 31 patients (mean age, 67.2 y) who underwent prostatectomy and preoperative PET were retrospectively analyzed. On PET, focally increased uptake in the prostate was suggestive of tumor. A region of interest was placed on the suggestive area to generate an SUVmax; a similar region of interest was placed on adjacent visually PN. Both PCA and PN were stained with monoclonal anti-PSMA antibody (clone 3E6, 1:100, M3620). Results: All intraprostatic PCA lesions on PET could be confirmed histopathologically. In PN sections (n = 31), median staining intensity was mild, median percentage of stained cells was 20% ± 14.24%, and median immunoreactive score (IRS) was 1. In PCA sections (n = 31), median IRS was 3, median staining intensity was strong, and median percentage of stained cells was 80% ± 16.46%. The mean SUVmax (±SD) of PCA (14.06 ± 15.56) was significantly higher than that of PN (2.43 ± 0.63; P < 0.001). Receiver-operating-characteristic curve analyses of the SUVmax of PCA, validated by immunohistochemical staining in 62 tissue samples, showed the best cutoff to be 3.15 (sensitivity, 97%; specificity, 90%; area under curve, 0.987). Applied to multifocal PCA, it resulted in sensitivity and specificity of 87% and 97% respectively. The mean SUVmax of PCA and PN for an IRS of less than 2 (n = 26; 2.52 ± 0.64) was significantly lower than the mean SUVmax for an IRS of 2 or more (n = 36; 12.38 ± 15.02; P < 0.001). The mean SUVmax was significantly lower in PCA samples with fewer than 50% stained cells (n = 30; 2.81 ± 2.35) than in samples with 50% or more (n = 32; 13.34 ± 15.55; P < 0.001). There was no correlation between the SUVmax of PCA and Gleason score (P = 0.54). Conclusion: This study showed that SUVmax on 68Ga-PSMA PET/CT correlates significantly with PSMA expression in primary PCA, enabling the detection of PCA with a high sensitivity and specificity.

Potential of asphericity as a novel diagnostic parameter in the evaluation of patients with 68Ga-PSMA-HBED-CC PET-positive prostate cancer lesions.

BACKGROUND: The aim of this study was to evaluate the diagnostic value of the asphericity (ASP) as a novel quantitative parameter, reflecting the spatial heterogeneity of tracer uptake, in the staging process of patients with 68Ga-PSMA-HBED-CC positron emission tomography (PET)-positive prostate cancer (PC). In this study, 37 patients (median age 72 years, range 52-82 years) with newly diagnosed PC, who received a 68Ga-PSMA-HBED-CC PET fused with computed tomography (68Ga-PSMA-PET/CT), a magnetic resonance imaging (MRI) of the prostate, and a core needle biopsy (within 74.2 ± 80.2 days) with an available Gleason score (GSc) were extracted from the local database. The ASP and the viable tumor volume (VTV) was calculated using the rover software (ABX GmbH, Radeberg, Germany), a segmentation tool for automated tumor volume delineation. Additionally, parameters including total lesion binding rate (TLB), maximum, mean and peak standardized uptake value (SUVmax/mean/peak), prostate-specific antigen (PSA), D'Amico classification, and prostate imaging reporting and data system (PI-RADS) were analyzed. RESULTS: The ASP mean differed significantly (p ≤ 0.05) between the different GSc groups: GSc 6-7: 11.9 ± 4.8%, GSc 8: 25.5 ± 4.8%, GSc 9-10: 33.3 ± 6.8%. A significant correlation between ASP and GSc (rho = 0.88; CI 0.78-0.94; p < 0.05) was measured. The ASP enabled an independent (p > 0.05) prediction of the GSc. A moderate correlation was measured between ASP and the D'Amico classification (rho = 0.6; CI 0.32-0.78; p < 0.05). The VTV showed a moderate correlation with the SUVmax (rho = 0.58; CI 0.32-0.76; p < 0.05) and the GSc (rho = 0.51; CI 0.23-0.72; p < 0.05). CONCLUSION: The asphericity in 68Ga-PSMA-PET could represent a promising novel quantitative parameter for an improved non-invasive tumor staging of patients with PC.

[68Ga]PSMA-HBED-CC Uptake in Osteolytic, Osteoblastic, and Bone Marrow Metastases of Prostate Cancer Patients.

PURPOSE: The aim of this study was to evaluate potential differences in "Glu-NH-CO-NH-Lys" radio-labeled with [68Ga]gallium N,N-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N-diacetic acid ([68Ga]PSMA-HBED-CC) uptake in osteolytic, osteoblastic, mixed, and bone marrow metastases in prostate cancer (PC) patients. PROCEDURES: This retrospective study was approved by the local ethics committee. Patients who received [68Ga]PSMA-HBED-CC positron emission tomography/computed tomography ([68Ga]PSMA-PET/CT) with at least one positive bone metastasis were included in this study. Only patients who have not received systemic therapy for their PC were included. Bone metastases had to be confirmed by at least one other imaging modality or follow-up investigation. The maximum standardized uptake value (SUVmax) and mean Hounsfield units (HUmean) of each metastasis were measured. Based on CT, each metastasis was classified as osteolytic (OL), osteoblastic (OB), bone marrow (BM), or mixed (M). RESULTS: One hundred fifty-four bone metastases in 30 patients were evaluated. Eighty out of 154 (51.9%) metastases were classified as OB, 21/154 (13.6%) as OL, 23/154 (14.9%) as M, and 30/154 (19.5%) as BM. The SUVmax for the different types of metastases were 10.6 ± 7.07 (OB), 24.0 ± 19.3 (OL), 16.0 ± 21.0 (M), and 14.7 ± 9.9 (BM). The SUVmax of OB vs. OL and OB vs. BM metastases differed significantly (p ≤ 0.025). A significant negative correlation between HUmean and SUVmax (r = -0.23, p < 0.05) was measured. CONCLUSIONS: [68Ga]PSMA-HBED-CC uptake is higher in osteolytic and bone marrow metastases compared to osteoblastic metastases. Information derived from [68Ga]PSMA-PET and CT complement each other for the reliable diagnosis of the different types of bone metastases in PC patients.