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.

The Ross Procedure in Adults: Long-Term Results of Homografts and Stentless Xenografts for Pulmonary Valve Replacement.

Background The Ross procedure is an established method to treat aortic valve disease, offering excellent hemodynamic characteristics, growth potential, low risk of thromboembolism and no need for anticoagulation. Limitation of homograft quality and availability led to the use of different stentless xenografts. Long-term outcome and implications are yet to be addressed. Methods Forty five adult patients (mean age 38.8 ± 9.6 years) with aortic valve stenosis and/or insufficiency, who underwent the Ross procedure between 1995 and 2002 were identified for long-term evaluation. Patients younger than 18 years, with previous heart surgery and endocarditis were excluded. Stentless xenografts were used in 22 cases (Group X) and homografts in 23 cases (Group H). After review of the patients' history, morbidity and mortality were analyzed and risk stratification was performed. Results Between groups, baseline characteristics and operative data did not differ significantly. Total follow-up was 621.0 patient-years and 98.8% complete. Overall freedom from reoperation at 15 years was 68.4 ± 10.6% in group X and 85. ± 7.9% in group H (p = 0.09), respectively. Freedom from aortic valve reoperation at 15 years was comparable (83.9 ± 8.5% in group X and 85.3 ± 7.9% in group H, p = 0.61), whereas freedom from pulmonary valve reoperation at 15 years was significantly lower in group X (78.9 ± 9.4% versus 100%, p = 0.02). Long-term survival at 15 years was 79.7 ± 9.3% in group X and 94.4 ± 5.4% in group H (p = 0.07), respectively. Conclusions Stentless xenografts used as pulmonary valve substitute in the Ross procedure led to lower freedom from pulmonary valve reoperation compared with homografts. Additionally, there was a trend to inferior long-term survival with xenografts. Therefore, homografts should remain the preferred option for pulmonary valve replacement in the Ross procedure.

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.

[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.