We evaluated the accuracy of PET/CT with 68 Ga-PSMA-HBED-CC-a 68 Ga-conjugated ligand of human prostate-specific membrane antigen (PSMA)-to localize cancer in the prostate and surrounding tissue at initial diagnosis. Methods: Twenty-one patients with biopsy-proven prostate cancer underwent 68 Ga-PSMA-HBED-CC ( 68 Ga-PSMA) PET/CT at a median of 4 d (range, 0-47 d) before radical prostatectomy. Based on a 6-segment model, the Gleason score and proportion of tumor tissue within each segment (segmental tumor burden, or STB) as determined by histopathology (STB HP ) were correlated with SUV max and STB as determined by different SUV cutoffs for 68 Ga-PSMA PET (STB ). Furthermore, the involvement of seminal vesicles and other extracapsular extension were assessed by histopathology and PET/CT. Results: Histopathology-positive segments (n 5 100 of 126; 79%) demonstrated a significantly higher mean ± SD SUV max (11.8 ± 7.6) than histopathology-negative segments (4.9 ± 2.9; P , 0.001). Receiver-operating-characteristic analysis revealed an optimal SUV max cutoff of 6.5 for discrimination of histopathology-positive segments from histopathology-negative segments (area under the curve, 0.84; P , 0.001), which gave 67% sensitivity, 92% specificity, a 97% positive predictive value, a 42% negative predictive value, and 72% accuracy. STB PET3 as determined by (2 · blood SUV) 1 (2 · SD) correlated best with STB HP (Pearson ρ 5 0.68; P , 0.001; mean difference ± SD, 19% ± 15%). PET/CT correctly detected invasion of seminal vesicles (n 5 11 of 21 patients; 52%) with 86% accuracy and tumor spread through the capsule (n 5 12; 57%) with 71% accuracy. Conclusion: 68 Ga-PSMA PET/CT accurately detected the location and extent of primary prostate cancer. Our preliminary findings warrant further investigation of 68 Ga-PSMA PET/CT in conjunction with needle biopsy.
BackgroundPET with O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) has reached increasing clinical significance for patients with brain neoplasms. For quantification of standard PET-derived parameters such as the tumor-to-background ratio, the background activity is assessed using a region of interest (ROI) or volume of interest (VOI) in unaffected brain tissue. However, there is no standardized approach regarding the assessment of the background reference. Therefore, we evaluated the intra- and inter-reader variability of commonly applied approaches for clinical 18F-FET PET reading.The background activity of 20 18F-FET PET scans was independently evaluated by 6 readers using a (i) simple 2D-ROI, (ii) spherical VOI with 3.0 cm diameter, and (iii) VOI consisting of crescent-shaped ROIs; each in the contralateral, non-affected hemisphere including white and gray matter in line with the European Association of Nuclear Medicine (EANM) and German guidelines. To assess intra-reader variability, each scan was evaluated 10 times by each reader. The coefficient of variation (CoV) was assessed for determination of intra- and inter-reader variability. In a second step, the best method was refined by instructions for a guided background activity assessment and validated by 10 further scans.ResultsCompared to the other approaches, the crescent-shaped VOIs revealed most stable results with the lowest intra-reader variabilities (median CoV 1.52%, spherical VOI 4.20%, 2D-ROI 3.69%; p < 0.001) and inter-reader variabilities (median CoV 2.14%, spherical VOI 4.02%, 2D-ROI 3.83%; p = 0.001). Using the guided background assessment, both intra-reader variabilities (median CoV 1.10%) and inter-reader variabilities (median CoV 1.19%) could be reduced even more.ConclusionsThe commonly applied methods for background activity assessment show different variability which might hamper 18F-FET PET quantification and comparability in multicenter settings. The proposed background activity assessment using a (guided) crescent-shaped VOI allows minimization of both intra- and inter-reader variability and might facilitate comprehensive methodological standardization of amino acid PET which is of interest in the light of the anticipated EANM technical guidelines.
Despite advances in diagnosis and the use of different therapeutic regimens in astrocytic high-grade glioma (HGG), the prognosis for patients remains grim. Additional pretherapeutic information is needed to tailor management. To gain additional prognostic information at primary diagnosis, we investigated the value ofWe retrospectively evaluated 121 patients who had a primary diagnosis of astrocytic HGG (51 World Health Organization [WHO] grade III; 70 WHO IV) and underwent dynamic 18 F-FET PET before histopathologic assessment. We assessed static parameters (maximal and mean tumoral standardized uptake value corrected for mean background activity in the contralateral hemisphere [SUV max / BG and SUV mean /BG, respectively], biologic tumor volume) and dynamic time-activity curves, including minimal time to peak (TTP min ). The prognostic influence of PET parameters and other clinical parameters on progression-free and overall survival was evaluated using uni-and multivariate Cox regression and Kaplan-Meier survival estimates. Results: In the group overall, median progression-free survival and overall survival were 12.2 and 21.9 mo. SUV max /BG, SUV mean /BG, and biologic tumor volume were significantly higher in WHO IV than in WHO III gliomas; median TTP min was 12.5 min in both groups. On univariate analysis, the factors age, WHO grade, O6-methylguanine-DNA methyltransferase promoter methylation status, contrast enhancement, initial treatment, and TTP min showed prognostic significance, with WHO grade, O6-methylguanine-DNA methyltransferase status, age, and TTP min remaining significant in the multivariate analysis. WHO grade and TTP min reached a similar fit for the prognostic evaluation. The prognosis of WHO III astrocytoma with an early TTP min of 12.5 min or less did not differ significantly from that of glioblastoma. Conclusion: Early TTP min is associated with worse outcome in patients with newly diagnosed astrocytic HGG. In the preoperative setting, TTP min can be a valuable noninvasive prognostic marker with comparable significance to WHO grade. Additionally, TTP min can help identify highly aggressive WHO III astrocytoma tumors and may help in adjusting standard treatment toward an individualized, risk-adapted therapy regime.
TAT. Newly diagnosed grade 1/2 xerostomia after TAT was observed in 5 patients. One patient reported no xerostomia at all. Conclusion:Our first clinical data for TAT using 225 Ac-PSMA-I&T showed promising antitumor effect in advanced mCRPC. These results are highly comparable to data on 225 Ac-PSMA-617 TAT.
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