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Background Multiparametric MRI (mpMRI) is effective for detecting prostate cancer (PCa); however, there is a high rate of equivocal Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions and false-positive findings. Purpose To investigate whether fluorine 18 ( 18 F) prostate-specific membrane antigen (PSMA) 1007 PET/CT after mpMRI can help detect localized clinically significant PCa (csPCa), particularly for equivocal PI-RADS 3 lesions. Materials and Methods This prospective study included participants with elevated prostate-specific antigen (PSA) levels referred for prostate mpMRI between September 2020 and February 2022. 18 F-PSMA-1007 PET/CT was performed within 30 days of mpMRI and before biopsy. PI-RADS category and level of suspicion (LOS) were assessed. PI-RADS 3 or higher lesions at mpMRI and/or LOS 3 or higher lesions at 18 F-PSMA-1007 PET/CT underwent targeted biopsies. PI-RADS 2 or lower and LOS 2 or lower lesions were considered nonsuspicious and were monitored during a 1-year follow-up by means of PSA testing. Diagnostic accuracy was assessed, with histologic examination serving as the reference standard. International Society of Urological Pathology (ISUP) grade 2 or higher was considered csPCa. Results Seventy-five participants (median age, 67 years [range, 52-77 years]) were assessed, with PI-RADS 1 or 2, PI-RADS 3, and PI-RADS 4 or 5 groups each including 25 participants. A total of 102 lesions were identified, of which 80 were PI-RADS 3 or higher and/or LOS 3 or higher and therefore underwent targeted biopsy. The per-participant sensitivity for the detection of csPCa was 95% and 91% for mpMRI and 18 F-PSMA-1007 PET/CT, respectively, with respective specificities of 45% and 62%. 18 F-PSMA-1007 PET/CT was used to correctly differentiate 17 of 26 PI-RADS 3 lesions (65%), with a negative and positive predictive value of 93% and 27%, respectively, for ruling out or detecting csPCa. One additional significant and one insignificant PCa lesion (PI-RADS 1 or 2) were found at 18 F-PSMA-1007 PET/CT that otherwise would have remained undetected. Two participants had ISUP 2 tumors without PSMA uptake that were missed at PET/CT. Conclusion 18 F-PSMA-1007 PET/CT showed good sensitivity and moderate specificity for the detection of csPCa and ruled this out in 93% of participants with PI-RADS 3 lesions. Clinical trial registration no. NCT04487847 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Turkbey in this issue.

Introduction: Prostate specific membrane antigen (PSMA) directed radioligand therapy (RLT) is a novel therapy for metastatic castration-resistant prostate cancer (mCRPC) patients. However, it is still poorly understood why approximately 40% of the patients does not respond to PSMA-RLT. The aims of this study were to evaluate the pretreatment PSMA expression on immunohistochemistry (IHC) and PSMA uptake on PET/CT imaging in mCRPC patients who underwent PSMA-RLT. We correlated these parameters and a cell proliferation marker (Ki67) to the therapeutic efficacy of PSMA-RLT., Patients and Methods: In this retrospective study, mCRPC patients who underwent PSMA-RLT were analyzed. Patients biopsies were scored for immunohistochemical Ki67 expression, PSMA staining intensity and percentage of cells with PSMA expression. Moreover, the PSMA tracer uptake of the tumor lesion(s) and healthy organs on PET/CT imaging was assessed. The primary outcome was to evaluate the association between histological PSMA protein expression of tumor in pre-PSMA-RLT biopsies and the PSMA uptake on PSMA PET/CT imaging of the biopsied lesion. Secondary outcomes were to assess the relationship between PSMA expression and Ki67 on IHC and the progression free survival (PFS) and overall survival (OS) following PSMA-RLT., Results: In total, 22 mCRPC patients were included in this study. Nineteen (86%) patients showed a high and homogenous PSMA expression of >80% on IHC. Three (14%) patients had low PSMA expression on IHC. Although there was limited PSMA uptake on PET/CT imaging, these 3 patients had lower PSMA uptake on PET/CT imaging compared to the patients with high PSMA expression on IHC. Yet, no correlation was found between PSMA uptake on PET/CT imaging and PSMA expression on IHC (SUVmax: R 2  = 0.046 and SUVavg: R 2  = 0.036). The 3 patients had a shorter PFS compared to the patients with high PSMA expression on IHC (HR: 4.76, 95% CI: 1.14-19.99; P = .033). Patients with low Ki67 expression had a longer PFS and OS compared to patients with a high Ki67 expression (HR: 0.40, 95% CI: 0.15-1.06; P = .013) CONCLUSION: The PSMA uptake on PSMA-PET/CT generally followed the PSMA expression on IHC. However, heterogeneity may be missed on PSMA-PET/CT. Immunohistochemical PSMA and Ki67 expression in fresh tumor biopsies, may contribute to predict treatment efficacy of PSMA-RLT in mCRPC patients. This needs to be further explored in prospective cohorts., Competing Interests: Disclosure The authors have declared that no competing interest exists., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Our purpose was to prospectively investigate optimal evaluation of qualitative and quantitative 18 F-FDG PET/CT in response evaluations 12-14 wk after neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer patients. Methods: This was a side study of the prospective diagnostic pre-SANO trial. 18 F-FDG PET/CT scans at baseline and at 12-14 wk after nCRT were qualitatively assessed for the presence of tumor. Maximum SUVs normalized for lean body mass (SUL max ) were measured in all scans. The primary endpoint was the proportion of false-negative patients with tumor regression grade (TRG) 3-4 (>10% vital residual tumor) in qualitative and quantitative analyses. Receiver-operating-characteristic curve analysis for TRG1 versus TRG3-4 using SUL max , SUL max tumor-to-esophagus ratio, and Δ%SUL max was performed to define optimal cutoffs. Secondary endpoints were sensitivity, specificity, negative predictive value, and positive predictive value for TRG1 versus TRG2-4. Results: In total, 129 of 219 patients were analyzed. Qualitative 18 F-FDG PET/CT was unable to detect TRG3-4 in 15% of patients. Sensitivity, specificity, negative predictive value, and positive predictive value in qualitative analysis for detecting TRG1 versus TRG2-4 was 80%, 37%, 42%, and 77%, respectively. In 18 of 190 patients (10%) with follow-up scans after nCRT, 18 F-FDG PET/CT identified new interval metastases. Quantitative parameters did not detect TRG3-4 tumor in 27%-61% of patients. The optimal cutoff for detecting TRG1 versus TRG2-4 was a post-nCRT SUL max of 2.93 (area under receiver-operating-characteristic curve, 0.70). Conclusion: Qualitative and quantitative analyses of 18 F-FDG PET/CT are unable to accurately detect TRG3-4 and to discriminate substantial residual disease from benign inflammation-induced 18 F-FDG uptake after nCRT. However, 18 F-FDG PET/CT is useful for the detection of interval metastases and might become useful in an active surveillance strategy with serial 18 F-FDG PET/CT scanning., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Static single-time-frame 18 F-FDG PET/CT is useful for the localization and functional characterization of pheochromocytomas and paragangliomas (PPGLs). 18 F-FDG uptake varies between PPGLs with different genotypes, and the highest SUVs are observed in cases of succinate dehydrogenase ( SDH ) mutations, possibly related to enhanced aerobic glycolysis in tumor cells. The exact determinants of 18 F-FDG accumulation in PPGLs are unknown. We performed dynamic PET/CT scanning to assess whether in vivo 18 F-FDG pharmacokinetics has added value over static PET to distinguish different genotypes. Methods: Dynamic 18 F-FDG PET/CT was performed on 13 sporadic PPGLs and 13 PPGLs from 11 patients with mutations in SDH complex subunits B and D, von Hippel-Lindau ( VHL ), RET, and neurofibromin 1 ( NF1 ). Pharmacokinetic analysis was performed using a 2-tissue-compartment tracer kinetic model. The derived transfer rate-constants for transmembranous glucose flux ( K 1 [in], k 2 [out]) and intracellular phosphorylation ( k 3 ), along with the vascular blood fraction (V b ), were analyzed using nonlinear regression analysis. Glucose metabolic rate (MR glc ) was calculated using Patlak linear regression analysis. The SUV max of the lesions was determined on additional static PET/CT images. Results: Both MR glc and SUV max were significantly higher for hereditary cluster 1 ( SDHx, VHL ) tumors than for hereditary cluster 2 ( RET, NF1 ) and sporadic tumors ( P < 0.01 and P < 0.05, respectively). Median k 3 was significantly higher for cluster 1 than for sporadic tumors ( P < 0.01). Median V b was significantly higher for cluster 1 than for cluster 2 tumors ( P < 0.01). No statistically significant differences in K 1 and k 2 were found between the groups. Cutoffs for k 3 to distinguish between cluster 1 and other tumors were established at 0.015 min -1 (100% sensitivity, 15.8% specificity) and 0.636 min -1 (100% specificity, 85.7% sensitivity). MR glc significantly correlated with SUV max ( P = 0.001) and k 3 ( P = 0.002). Conclusion: In vivo metabolic tumor profiling in patients with PPGL can be achieved by assessing 18 F-FDG pharmacokinetics using dynamic PET/CT scanning. Cluster 1 PPGLs can be reliably identified by a high 18 F-FDG phosphorylation rate., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: The aim of this study was to determine the diagnostic value of 18 F-fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET/CT) and magnetic resonance imaging (MRI) in diagnosing vertebral osteomyelitis., Methods: From November 2015 until December 2016, 32 patients with suspected vertebral osteomyelitis were prospectively included. All patients underwent both 18 F-FDG-PET/CT and MRI within 48 h. All images were independently reevaluated by two radiologists and two nuclear medicine physicians who were blinded to each others' image interpretation. 18 F-FDG-PET/CT and MRI were compared to the clinical diagnosis according to international guidelines., Results: For 18 F-FDG-PET/CT, sensitivity, specificity, PPV, and NPV in diagnosing vertebral osteomyelitis were 100%, 83.3%, 90.9%, and 100%, respectively. For MRI, sensitivity, specificity, PPV, and NPV were 100%, 91.7%, 95.2%, and 100%, respectively. MRI detected more epidural/spinal abscesses. An important advantage of 18 F-FDG-PET/CT is the detection of metastatic infection (16 patients, 50.0%)., Conclusion: 18 F-FDG-PET/CT and MRI are both necessary techniques in diagnosing vertebral osteomyelitis. An important advantage of 18 F-FDG-PET/CT is the visualization of metastatic infection, especially in patients with bacteremia. MRI is more sensitive in detection of small epidural abscesses.

Metastatic infection is an important complication of Staphylococcus aureus bacteremia (SAB). Early diagnosis of metastatic infection is crucial, because specific treatment is required. However, metastatic infection can be asymptomatic and difficult to detect. In this study, we investigated the role of 18 F-FDG PET/CT in patients with SAB for detection of metastatic infection and its consequences for treatment and outcome. Methods: All patients with SAB at Radboud University Medical Center were included between January 2013 and April 2016. Clinical data and results of 18 F-FDG PET/CT and other imaging techniques, including echocardiography, were collected. Primary outcomes were newly diagnosed metastatic infection by 18 F-FDG PET/CT, subsequent treatment modifications, and patient outcome. Results: A total of 184 patients were included, and 18 F-FDG PET/CT was performed in 105 patients, of whom 99 had a high-risk bacteremia. 18 F-FDG PET/CT detected metastatic infectious foci in 73.7% of these high-risk patients. In 71.2% of patients with metastatic infection, no signs and symptoms suggesting metastatic complications were present before 18 F-FDG PET/CT was performed. 18 F-FDG PET/CT led to a total of 104 treatment modifications in 74 patients. Three-month mortality was higher in high-risk bacteremia patients without 18 F-FDG PET/CT performed than in those in whom 18 F-FDG PET/CT was performed (32.7% vs. 12.4%, P = 0.003). In multivariate analysis, 18 F-FDG PET/CT was the only factor independently associated with reduced mortality ( P = 0.005; odds ratio, 0.204; 95% confidence interval, 0.066-0.624). A higher comorbidity score was independently associated with increased mortality ( P = 0.003; odds ratio, 1.254; 95% confidence interval, 1.078-1.457). Conclusion: 18 F-FDG PET/CT is a valuable technique for early detection of metastatic infectious foci, often leading to treatment modification. Performing 18 F-FDG PET/CT is associated with significantly reduced 3-mo mortality., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)