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Purpose: PET/MRI has recently been introduced into clinical practice. We prospectively investigated the clinical impact of PET/MRI compared with PET/CT, in a mixed population of cancer patients, and performed an economic evaluation of PET/MRI., Methods: Cancer patients referred for routine staging or follow-up by PET/CT underwent consecutive PET/CT and PET/MRI, using single applications of [ 18 F]FDG, [ 68 Ga]Ga-DOTANOC, or [ 18 F]FDOPA, depending on tumor histology. PET/MRI and PET/CT were rated separately, and lesions were assessed per anatomic region; based on regions, per-examination and per-patient accuracies were determined. A simulated, multidisciplinary team meeting served as reference standard and determined whether differences between PET/CT and PET/MRI affected patient management. The McNemar tests were used to compare accuracies, and incremental cost-effectiveness ratios (ICERs) for PET/MRI were calculated., Results: Two hundred sixty-three patients (330 same-day PET/CT and PET/MRI examinations) were included. PET/MRI was accurate in 319/330 examinations and PET/CT in 277/330 examinations; the respective accuracies of 97.3% and 83.9% differed significantly (P < 0.001). The additional findings on PET/MRI-mainly liver and brain metastases-had implications for patient management in 21/263 patients (8.0%). The per-examination cost was 596.97 EUR for PET/MRI and 405.95 EUR for PET/CT. ICERs for PET/MRI were 14.26 EUR per percent of diagnostic accuracy and 23.88 EUR per percent of correctly managed patients., Conclusions: PET/MRI enables more appropriate management than PET/CT in a nonnegligible fraction of cancer patients. Since the per-examination cost is about 50% higher for PET/MRI than for PET/CT, a histology-based triage of patients to either PET/MRI or PET/CT may be meaningful.

Purpose: In PIK3CA mutant breast cancer, downstream hyperactivation of the PI3K/AKT/mTOR pathway may be associated with increased glycolysis of cancer cells. The purpose of this study was to investigate the functional association of PIK3CA mutational status and tumor glycolysis in invasive ER+/HER2- early breast cancer., Procedures: This institutional review board-approved retrospective study included a dataset of 67 ER+/HER2- early breast cancer patients. All patients underwent 2-deoxy-2-[ 18 F]fluoro-D-glucose positron emission tomography/X-ray computed tomography ([ 18 F]FDG PET/CT) and clinico-pathologic assessments as part of a prospective study. For this retrospective analysis, pyrosequencing was used to detect PIK3CA mutations of exons 4, 7, 9, and 20. Tumor glucose metabolism was assessed semi-quantitatively with [ 18 F]FDG PET/CT using maximum standardized uptake values (SUV max ). SUV max values were corrected for the partial volume effect, and metabolic tumor volume was calculated using the volume of interest automated lesion growing function 2D tumor size, i.e., maximum tumor diameter was assessed on concurrent pre-treatment contrast-enhanced magnetic resonance imaging., Results: PIK3CA mutations were present in 45 % of all tumors. Mutations were associated with a small tumor diameter (p < 0.01) and with low nuclear grade (p = 0.04). Glycolytic activity was positively associated with nuclear grade (p = 0.01), proliferation (p = 0.002), regional lymph node metastasis (p = 0.015), and metabolic tumor volume (p = 0.001) but not with tumor size/T-stage. In invasive ductal carcinomas, median SUV max was increased in PIK3CA-mutated compared to wild-type tumors; however, this increase did not reach statistical significance (p = 0.05). Multivariate analysis of invasive ductal carcinomas revealed [ 18 F]FDG uptake to be independently associated with PIK3CA status (p = 0.002) and nuclear tumor grade (p = 0.046). Size, volume, and regional nodal status had no influence on glycolytic activity. PIK3CA mutational status did not influence glycolytic metabolism in lobular carcinomas. Glycolytic activity and PIK3CA mutational status had no significant influence on recurrence-free survival or disease-specific survival., Conclusions: In ER+/HER2- invasive ductal carcinomas of the breast, glucose uptake is independently associated with PIK3CA mutations. Initial data suggest that [ 18 F]FDG uptake reflects complex genomic alterations and may have the potential to be used as candidate biomarker for monitoring therapeutic response and resistance mechanisms in emerging therapies that target the PI3K/AKT/mTOR pathway.

In rheumatoid arthritis (RA), chronic joint inflammation leading to bone and cartilage damage is the major cause of functional impairment. Whereas reduction of synovitis and blockade of joint damage can be successfully achieved by disease modifying antirheumatic therapies, bone repair upon therapeutic interventions has only been rarely reported. The aim of this study was to use fluorodeoxyglucose ([ 18 F]FDG) and [ 18 F]fluoride µPET/CT imaging to monitor systemic inflammatory and destructive bone remodeling processes as well as potential bone repair in an established mouse model of chronic inflammatory, erosive polyarthritis. Therefore, human tumor necrosis factor transgenic (hTNFtg) mice were treated with infliximab, an anti-TNF antibody, for 4 weeks. Before and after treatment period, mice received either [ 18 F]FDG, for detecting inflammatory processes, or [ 18 F]fluoride, for monitoring bone remodeling processes, for PET scans followed by CT scans. Standardized uptake values (SUV mean ) were analyzed in various joints and histopathological signs of arthritis, joint damage, and repair were assessed. Longitudinal PET/CT scans revealed a significant decrease in [ 18 F]FDG SUVs in affected joints demonstrating complete remission of inflammatory processes due to TNF blockade. In contrast, [ 18 F]fluoride SUVs could not discriminate between different severities of bone damage in hTNFtg mice. Repeated in vivo CT images proved a structural reversal of preexisting bone erosions after anti-TNF therapy. Accordingly, histological analysis showed complete resolution of synovial inflammation and healing of bone at sites of former bone erosion. We conclude that in vivo multimodal [ 18 F]FDG µPET/CT imaging allows to quantify and monitor inflammation-mediated bone damage and reveals not only reversal of synovitis but also bone repair upon TNF blockade in experimental arthritis. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc., (© 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.)

Purpose: To assess the accuracy of [ 68 Ga]-PSMA-11 PET/CT or [ 68 Ga]-PSMA-11 PET/MRI (PSMA-11 PET/CT(MRI)) for lymph node (LN) staging using salvage LN dissection (SLND) in patients with biochemical recurrence (BCR) after radical prostatectomy (RP)., Patients and Methods: In a prospective study, 65 consecutive patients who developed BCR after RP underwent SLND after PSMA-11 PET/CT(MRI) between 2014 and 2018. Extended SLND up to the inferior mesenteric artery was performed in all patients. Regional and template-based correlations between the presence of LN metastases on histopathology and whole-body PSMA-11 PET/CT(MRI) results were evaluated. The diagnostic accuracy of PSMA-11 PET/CT(MRI) was also evaluated in relation to PSA level at the time of SLND., Results: The median age of the patients at the time of SLND was 65 years (IQR 63-69 years) and the median PSA level was 1.4 ng/ml (IQR 0.8-2.9 ng/ml). Before SLND, 50 patients (77%) had additional therapy after RP (26.2% androgen-deprivation therapy and 50.8% radiotherapy). The median number of LNs removed on SLND was 40 (IQR 33-48) and the median number of positive nodes was 4 (IQR 2-6). LN metastases were seen in 13.8% of resected LNs (317 of 2,292). LNs positive on PSMA-11 PET/CT(MRI) had a median diameter of 7.2 mm (IQR 5.3-9 mm). Metastatic LNs in regions negative on PSMA-11 PET had a median diameter of 3.4 mm (IQR 2.1-5.4 mm). In a regional analysis, the sensitivity of PSMA-11 PET/CT(MRI) ranged from 72% to 100%, and the specificity from 96% to 100%. Region-specific positive and negative predictive values ranged from 95% to 100% and 93% to 100%, respectively., Conclusion: PSMA-11 PET/CT(MRI) has a very good performance for the identification of LN metastases in patients with BCR after RP. The high diagnostic accuracy in the regional and subregional analyses demonstrates the potential of this approach to enable a region-directed instead of a complete bilateral therapeutic intervention. The performance of PSMA-11 PET/CT(MRI) is dependent on the PSA level and the size of the metastatic deposit.

Purpose: The aim of this study was to compare the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, the immune RECIST (iRECIST) criteria, and the Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) 1.0 in patients with advanced non-small cell lung cancer treated with programmed cell death protein 1 (PD-1)/programmed cell death protein 1 ligand (PD-L1) inhibitors., Methods: This prospective study of 42 patients treated with a PD-1/PD-L1 inhibitor was approved by our institutional review board, and all patients gave written, informed consent. Tumor burden dynamics were assessed on F-FDG PET/CT before and after treatment initiation. Immunotherapeutic responses were evaluated according to RECIST 1.1, iRECIST, and PERCIST 1.0 for the dichotomous groups, responders versus nonresponders. Cohen κ and Wilcoxon signed rank tests were used to evaluate concordance among these criteria. We assessed progression-free survival and overall survival using the Kaplan-Meier estimator., Results: The RECIST 1.1 and PERCIST 1.0 response classifications were discordant in 6 patients (14.2%; κ = 0.581). RECIST 1.1 and iRECIST were discordant in 2 patients, who evidenced pseudoprogression after treatment initiation. Median progression-free survival, as well as overall survival, was significantly longer for responders compared with nonresponders for all criteria (P < 0.001), with no significant difference between the 3 criteria (P > 0.05)., Conclusions: RECIST 1.1 and PERCIST 1.0 show only moderate agreement, but both can predict treatment response to PD-1/PD-L1 inhibitor therapy. In case of pseudoprogression, metabolic tumor activity may help to correctly classify treatment response.

Background: [ 18 F]-2-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (FDG-PET/CT) imaging provides important information about the size and metabolic activity of lesions caused by Echinococcus multilocularis and is therefore recommended for the initial assessment and follow-up of human alveolar echinococcosis (AE). The introduction of positron emission tomography/magnetic resonance imaging (PET/MRI) into clinical practice in affluent health care systems provides an alternative dual imaging modality, which has not yet been evaluated for AE., Objective: Here, we describe the initial clinical experience with comparative PET/CT and PET/MR imaging in four human AE patients at an Austrian reference centre., Results: PET/MR imaging showed comparable diagnostic capacity for liver lesions attributable to E. multilocularis infection, with a discrepancy only in the assessment of calcifications in one patient. Effective doses of radiation were 30.4-31 mSV for PET/CT, which were reduced in PET/MRI to the exposure of 18 F-FDG only (4.9-5.5 mSv)., Conclusions: PET/MRI provides comparable diagnostic information for AE management. The reduction in radiation exposure compared to PET/CT may be of particular importance for children and young patients not amenable for curative surgery requiring repeated long-term follow-up with dual imaging modalities. Further studies are warranted to prospectively evaluate the potential of PET/MRI in the management of AE., (© 2019 John Wiley & Sons Ltd.)

Purpose: The first aim of this study was to evaluate 68 Ga-PSMA HBED-CC conjugate 11 positron emission tomography (PSMA PET) parameters for assessment of response to 177 Lu-PSMA-617 radioligand therapy (RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC). The second aim was to investigate factors associated with overall survival (OS)., Methods: We retrospectively assessed mean standardized uptake values (SUVmean) and total tumor volumes (TTV) on PSMA PET in 38 of 55 mCRPC patients before and after RLT. PSA testing and PSMA PET/CT(MRI) imaging were performed during the 8 weeks before and the 6 weeks after RLT. PSMA PET and CT(MRI) images were reviewed separately according to the modified PET Response Criteria in Solid Tumors (mPERCIST) and RECIST1.1. The results were compared with PSA responses. Associations between OS and the RECIST evaluation and changes in SUVmean, TTV, and PSA, CRP, LDH, hemoglobin and ALP levels were determined in a univariable survival analysis., Results: The median PSA level at the time of pretherapy PSMA PET/CT(MRI) was 60.8 ng/ml (IQR 15.4, 264.2 ng/ml). After RLT the median PSA level decreased by 44%, TTV by 45.1%, SUVmean by 25.8% and RECIST by 11.3%. A PSA response was seen in 18 patients (47.4%), stable disease in 12 (31.6%) and progressive disease in 8 (21.1%). Contrary to the changes in SUVmean and the RECIST evaluation, the change in TTV was significantly associated with PSA response (p = 0.15, p = 0.58, and p < 0.001, respectively). After a median follow-up of 17 months (IQR 8.0, 24.2 months), 11 patients (28.9%) had died of their prostate cancer. The changes in both TTV and PSA levels were associated with OS (HR 1.001, 95% CI 1-1.003, p = 0.04, and HR 1.004, 95% CI 1.001-1.008, p = 0.01, respectively), while the changes in SUVmean and the RECIST evaluation were not. The pre-therapy CRP level was also associated with OS (HR 1.07, 95% CI 1.009-1.14, p = 0.02)., Conclusion: TTV on PSMA PET seems to be a reliable parameter for response assessment in mCRPC patients undergoing RLT and might overcome the limitations of RECIST in prostate cancer. Furthermore, the change in TTV was significantly associated with OS in our cohort.

Background: The objective of this study was to characterize tumor activity and mineralization status in newly-detected multiple myeloma (MM) bone lesions using 2- 18 F-fluoro-2-deoxy-D-glucose ( 18 F-FDG)-PET/CT and 18 F-sodium fluoride ( 18 F-NaF)-PET/CT before and after antitumor treatment., Materials and Methods: In this retrospective study, seven patients with histologically-verified MM were included (four women, three men; median age=57 years, standard deviation=11.23 years). PET/CT was performed with 18 F-FDG and with 18 F-NaF, both at baseline and after treatment. All patients had positive scans. Volumes of interest (VOIs) were drawn over all 18 F-FDG-PET/CT-positive bone lesions, as well as the corresponding regions in 18 F-NaF-PET/CT. For characterization of bone lesions, semi-quantitative standard uptake value (SUV) parameters were measured., Results: 18 F-FDG-PET/CT in the seven patients detected 39 metabolically active lesions that were correlated with the corresponding sites in 18 F-fluoride-PET/CT. Overall, the lesions showed a response to therapy, with a significant decrease in SUV max on PET/CT using 18 F-FDG (p<0.001) and with 18 F-NaF (p<0.001). In four patients with a second follow-up scan (at a median of 17 months after baseline scan), there was no significant change in lesion uptake., Conclusion: Based on our data, antitumor therapy in MM reduces not only tumor activity, but also the mineralization status of bone lesions. A second follow-up scan in a subset of the cohort yielded no change in mineralization status., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: To investigate [ 11 C]acetate PET-surrogate parameter of fatty acid synthase activity-as suitable tool for diagnosis and monitoring of liver steatosis., Methods: In this retrospective study, data were obtained from 83 prostatic carcinoma patients from 1/2008 to 1/2014. Mean HU was calculated from unenhanced CT of all patients from liver with liver HU less than 40 as threshold for liver steatosis. SUV max of the liver and of the blood pool in thoracic aorta (as background for calculation of a liver/background ratio [SUV l/b ]) was measured. t test was used with a P < 0.05 considered as statistically significant difference and ROC analysis was used for calculating specificity and sensitivity., Results: 19/83 patients (20%) had diagnosis of hepatic steatosis according to CT. Uptake of [ 11 C]acetate was significantly higher in patients with hepatic steatosis as compared to control group (SUV max 7.96 ± 2.0 vs. 5.48 ± 2.3 [P < 0.001]). There was also a significant correlation between both SUV max (r = - 0.52, P < 0.001) and SUV l/b (r = - 0.59, P < 0.001) with the density (HU) of the liver. In ROC analysis for detection of liver steatosis SUV max (threshold: 5.86) had a sensitivity of 94% and specificity of 69% with an AUC of 0.81. Increasing body mass index is correlated with the severity of steatosis., Conclusion: We showed for the first time that hepatic steatosis associates with increased [ 11 C]acetate uptake. Also, severity of steatosis correlates with [ 11 C]acetate uptake. [ 11 C]acetate uptake PET seems promising for the assessment of liver steatosis.

Aim: We evaluated the clinical usefulness of 6-[ 18 F]fluoro-3,4-dihydroxy-L-phenylalanine( 18 F-FDOPA)-positron-emission tomography (PET)/computed tomography (CT) in insulinoma detection with contrast enhancement, early acquisition time, and no carbidopa premedication., Patients and Methods: Twenty-six patients diagnosed with hyperinsulinemic hypoglycemia underwent an 18 F-FDOPA PET/CT examination. Patients without carbidopa premedication and contrast-enhanced CT were included. Imaging findings were compared to the overall final diagnosis (histological findings)., Results: In 10 of 26 patients (eight women, two men; mean age=53 years; age range=30-94 years), a detected lesion was confirmed histologically as an insulinoma. 18 F-FDOPA PET detected the tumor in five out of ten patients. Contrast-enhanced CT also detected the tumor in five out of ten. Overall, 18 F-FDOPA PET/CT, with contrast enhancement and without carbidopa premedication, was able to detect the insulinoma in seven out of ten patients (70%)., Conclusion: Based on our data, 18 F-DOPA PET/CT, with contrast enhancement and without carbidopa premedication, as a 'one-stop' diagnostic modality is a viable option for insulinoma detection., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The aim of this study was to evaluate whether MP [11C]Acetate PET-MRI enables an accurate differentiation of benign and malignant prostate tumors as well as local and distant staging., Materials and Methods: Fifty-six consecutive patients fulfilling the following criteria were included in this IRB-approved prospective study: elevated PSA levels or suspicious findings at digital rectal examination or TRUS; and histopathological verification. All patients underwent MP [11C]Acetate PET-MRI of the prostate performed on separate scanners with PET/CT using [11C]Acetate and 3T MP MR imaging. Appropriate statistical tests were used to determine diagnostic accuracy, local and distant staging., Results: MP imaging with two MRI parameters (T2w and DWI) achieved the highest sensitivity, specificity, and diagnostic accuracy of 95%, 68.8%, and 88%, with an AUC of 0.82 for primary PCa detection. Neither assessments with a single parameter (AUC, 0.54-0.79), nor different combinations with up to five parameters (AUC, 0.67-0.79) achieved equally good results. MP [11C]Acetate PET-MRI improved local staging with a sensitivity, specificity, and diagnostic accuracy of 100%, 96%, and 97% compared to MRI alone with 72.2%, 100%, and 95.5%. MP [11C]Acetate PET-MRI correctly detected osseous and liver metastases in five patients., Conclusions: MP [11C]Acetate PET-MRI merges morphologic with functional information, and allows insights into tumor biology. MP [11C]Acetate PET-MRI with two MRI-derived parameters (T2 and DWI) yields the highest diagnostic accuracy. The addition of more parameters does not improve diagnostic accuracy of primary PCa detection. MP [11C]Acetate PET-MRI facilitates improved local and distant staging, providing "one-stop" staging in patients with primary PCa, and therefore has the potential to improve therapy., Patient Summary: In this report we investigated MP [11C]Acetate PET-MRI for detection, local and distant staging of prostate cancer. We demonstrate that MP [11C]Acetate PET-MRI with two MRI-derived parameters (T2 and DWI) achieves the best diagnostic accuracy for primary prostate cancer detection and that MP [11C]Acetate PET-MRI enables an improved local and distant staging.

Background parenchymal enhancement (BPE), and the amount of fibroglandular tissue (FGT) assessed with MRI have been implicated as sensitive imaging biomarkers for breast cancer. The purpose of this study was to quantitatively assess breast parenchymal uptake (BPU) on 18 F-FDG PET/CT as another valuable imaging biomarker and examine its correlation with BPE, FGT, and age., Methods: This study included 129 patients with suspected breast cancer and normal imaging findings in one breast (BI-RADS 1), whose cases were retrospectively analyzed. All patients underwent prone 18 F-FDG PET/CT and 3-T contrast-enhanced MRI of the breast. In all patients, interpreter 1 assessed BPU quantitatively using SUV max Interpreters 1 and 2 assessed amount of FGT and BPE in the normal contralateral breast by subjective visual estimation, as recommended by BI-RADS. Interpreter 1 reassessed all cases and repeated the BPU measurements. Statistical tests were used to assess correlations between BPU, BPE, FGT, and age, as well as inter- and intrainterpreter agreement., Results: BPU on 18 F-FDG PET/CT varied among patients. The mean BPU SUV max ± SD was 1.57 ± 0.6 for patients with minimal BPE, 1.93 ± 0.6 for mild BPE, 2.42 ± 0.5 for moderate BPE, and 1.45 ± 0.3 for marked BPE. There were significant (P < 0.001) moderate to strong correlations among BPU, BPE, and FGT. BPU directly correlated with both BPE and FGT on MRI. Patient age showed a moderate to strong indirect correlation with all 3 imaging-derived tissue biomarkers. The coefficient of variation for quantitative BPU measurements with SUV max was 5.6%, indicating a high reproducibility. Interinterpreter and intrainterpreter agreement for BPE and FGT was almost perfect, with a κ-value of 0.860 and 0.822, respectively., Conclusion: The results of our study demonstrate that BPU varied among patients. BPU directly correlated with both BPE and FGT on MRI, and BPU measurements were highly reproducible. Patient age showed a strong inverse correlation with all 3 imaging-derived tissue biomarkers. These findings indicate that BPU may serve as a sensitive imaging biomarker for breast cancer prediction, prognosis, and risk assessment., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Purpose: PET with (18)F-FDG has the potential to assess vascular macrophage metabolism. (18)F-FDG is most often used in combination with contrast-enhanced CT to localize increased metabolism to specific arterial lesions. Novel (18)F-FDG PET/MRI hybrid imaging shows high potential for the combined evaluation of atherosclerotic plaques, due to the superior morphological conspicuity of plaque lesions. The purpose of this study was to evaluate the reliability and accuracy of (18)F-FDG PET/MRI uptake quantification compared to PET/CT as a reference standard in patients with carotid atherosclerotic plaques., Methods: The study group comprised 34 consecutive oncological patients with carotid plaques who underwent both PET/CT and PET/MRI with (18)F-FDG on the same day. The presence of atherosclerotic plaques was confirmed by 3 T MRI scans. Maximum standardized uptake values (SUVmax) for carotid plaque lesions and the average SUV of the blood pool within the adjacent internal jugular vein were determined and target-to-blood ratios (TBRs, plaque to blood pool) were calculated., Results: Atherosclerotic lesions with maximum colocalized focal FDG uptake were assessed in each patient. SUVmax values of carotid plaque lesions were significantly lower on PET/MRI than on PET/CT (2.3 ± 0.6 vs. 3.1 ± 0.6; P < 0.01), but were significantly correlated between PET/CT and PET/MRI (Spearman's r = 0.67, P < 0.01). In contrast, TBRmax values of plaque lesions were similar on PET/MRI and on PET/CT (2.2 ± 0.3 vs. 2.2 ± 0.3; P = 0.4), and again were significantly correlated between PET/MRI and PET/CT (Spearman's r = 0.73, P < 0.01). Considering the increasing trend in SUVmax and TBRmax values from early to delayed imaging time-points on PET/CT and PET/MRI, respectively, with continuous clearance of radioactivity from the blood, a slight underestimation of TBRmax values may also be expected with PET/MRI compared with PET/CT., Conclusion: SUVmax and TBRmax values are widely accepted reference parameters for estimation of the radioactivity of atherosclerotic plaques on PET/CT. However, due to a systematic underestimation of SUVmax and TBRmax with PET/MRI, the optimal cut-off values indicating the presence of inflamed plaque tissue need to be newly defined for PET/MRI.