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Purpose: Dynamic PET/CT scan of 68Ga-FAPI-04 in patients with suspected malignant hepatic lesions were retrospectively analyzed to find the optimal acquisition time with better lesion detection rate. Methods: Twenty-two patients with lesions confirmed by CT or MRI were performed with dynamic 68Ga-FAPI-04 PET/CT scan. Tracer uptake of lesions and normal organs at different time points were analyzed. Standardized uptake value (SUV) and tumor-to-background (TBR) were calculated based on the quantification of images. Results: SUV of normal organs decreased rapidly from 10 to 30 min and decreased gradually from 30 to 60 min. Besides, the uterus showed a particularly high uptake in all patients (12.62 ± 4.58 at 10 min p.i., 12.04 ± 3.99 at 30 min p.i., 10.92 ± 2.38 at 60 min p.i.). SUV of lesions decreased gradually, while TBR increased from 10- to 60-min post-injection. Visual analysis verified a comparable lesion detectability of 30 min and 60 min with images of 10 min showing a decreased lesion detection number. Conclusion: This study revealed that similar detection rates were achieved at both 30 and 60 min, suggesting a static scan at 30 min to be appropriate in the clinic. Besides, although with high lesion uptake, early 68Ga-FAPI-04 PET imaging at 10 min after tracer injection could cause missed lesion detection. [ABSTRACT FROM AUTHOR]

Purpose: To determine the optimal imaging tool for clinical evaluation of pancreatic neoplasm by comparing the performance of 18F-FDG PET/MRI and PET/CT.Procedures: Patients with suspected pancreatic neoplasms underwent PET/MRI and PET/CT in the same day prior to resection or endoscopic ultrasound-guided fine-needle aspiration. Histology served as the golden standard of lesion classification. Visual assessment on lesion type and lesion malignancy via PET/MRI and PET/CT images was compared. Standard uptake values (SUVs) of PET images from the two scanners were measured and their correlations were further evaluated.Results: Thirty-nine patients were included for the final analysis. In visual assessment, we found MRI achieved better performance than CT in differentiating solid and cystic neoplasms, with accuracy of 100% vs. 87%, respectively. In visual malignancy diagnosis, the accuracy of PET/CT was 92.3% for overall lesions and 90.9% for cysts, while the accuracy of PET/MRI was 92.3% and 86.4%, respectively. Besides, semi-quantitative analysis achieved better specificity than visual assessment for both hybrid modalities (100% vs. 87.5% for PET/CT; 100% vs. 81.5% for PET/MR). Furthermore, strong correlation of SUV was found between PET/CT and PET/MRI, with Pearson's correlation coefficients > 0.82.Conclusions: In this study, we found PET/MRI and PET/CT, both using 18F-FDG as tracer, had comparable overall performance in identification of pancreatic neoplasms. Interestingly, for patients who had suspected pancreatic neoplasm but invisible FDG uptake, PET/MRI had shown exceptionally better performance, probably because MR images could detect tiny abnormal structures to improve diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this meta-analysis was to estimate the clinical use value of 11C-FMZ and 18F-FDG in PET for the localization of epileptogenic zone and to provide evidence for practitioners' clinical decision-making. Methods: We searched PubMed and Embase in a time frame from inception to May 31, 2020. Studies utilizing FMZ or FDG-PET or FDG-PET/MRI used in patients with epilepsy, with EEG or surgical outcomes as the gold standard and corresponding outcomes such as concordance rates of PET or PET/MRI scan compared with reference standard, absolute numbers of participants with true-positive (TP), false-positive (FP), true-negative (TN), and false-negative (FN) results in FDG or FMZ PET. Pooled concordance rates, overall sensitivity, and specificity of 11C-FMZ-PET and 18F-FDG-PET were calculated. Results: In total, 44 studies met the inclusion criteria. The pooled concordance rates of FDG-PET, FMZ-PET, and FDG-PET/MRI coregistration compared with reference standard were 0.67 (95% CI: 0.60–0.73), 0.75 (95% CI: 0.57–0.93), and 0.93 (95% CI: 0.89–0.97), respectively. The concordance rate of 18F-FDG-PET in patients with temporal lobe epilepsy (TLE) was 0.79 (0.63; 0.92). The overall sensitivity and specificity of 18F-FDG-PET were 0.66 (95% CI: 0.58–0.73) and 0.71 (95% CI: 0.63–0.78), respectively. 11C-FMZ-PET displayed an overall sensitivity of 0.62 (95% CI: 0.49–0.73) and specificity of 0.73 (95% CI: 0.59–0.84). Conclusions: Both 11C-FMZ PET and 18F-FDG PET are the choice of modalities for the localization of epileptogenic zone, especially when coregistered with MRI. Key Points: •11C-FMZ-PET may be more helpful than18F-FDG-PET in the localization of epilepsy foci. • Coregistration of FDG-PET and MRI is recommended in the localization of epileptogenic zone. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to compare the performance of 68Ga-labelled fibroblast activating protein inhibitor (FAPI) PET and 18F-FDG PET for imaging of hepatic tumours. Methods: We prospectively assessed 20 patients with suspected intrahepatic lesions. Tumour radiological features, pathology, or follow-up examinations were assessed as ground truth in correlation with PET scans. Semiquantitative analysis was additionally performed by measuring the standardised uptake value (SUV). Tumour-to-liver background ratios (TBR) were calculated and compared between 68Ga-FAPI PET and 18F-FDG PET. FAPI expression was assessed by immunochemistry in samples obtained from 7 patients with hepatocellular carcinomas (HCC)/intrahepatic cholangiocarcinoma (ICC) or granulomas. Results: Primary intrahepatic tumours, including 16 HCC in 14 patients and 4 ICC in 3 patients with extrahepatic metastases, were determined by histology (n = 14) and clinical examinations (n = 3). Based on visual analysis, 17 patients presented elevated 68Ga-FAPI uptake (sensitivity: 100%, specificity: 100%), while 7 patients presented 18F-FDG avid tumours (sensitivity: 58.8%, specificity: 100%). 68Ga-FAPI PET/CT identified 17 extrahepatic metastases vs. 13 in 18F-FDG PET/CT in 2 ICC patients. Three benign liver nodules in three patients showed negligible uptake in dual-PET scans. The SUVmax_HCC = 8.47 ± 4.06 and TBRmax_HCC = 7.13 ± 5.52, and SUVmax_ICC = 14.14 ± 2.20 TBRmax_ICC = 26.46 ± 4.94 in 68Ga-FAPI-04 PET/CT were significantly higher than the 18F-FDG uptake presenting SUVmax_HCC = 4.86 ± 3.58 and TBRmax_HCC = 2.39 ± 2.21, and SUVmax_ICC = 9.19 ± 3.60 and TBRmax_ICC = 2.39 ± 2.21 (all p values < 0.05). ICC patients showed higher levels of FAPI uptake in the primary hepatic lesions compared to extrahepatic metastases, TBRmax_ICC = 15.18 ± 5.80 (p = 0.04). Conclusions: 68Ga-FAPI PET-CT has superior potential in the detection of primary hepatic malignancy compared to 18F-FDG. [ABSTRACT FROM AUTHOR]

Purpose: To develop and validate a machine learning model based on radiomic features derived from 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) images to preoperatively predict the pathological grade in patients with pancreatic ductal adenocarcinoma (PDAC). Methods: A total of 149 patients (83 men, 66 women, mean age 61 years old) with pathologically proven PDAC and a preoperative 18F-FDG PET/CT scan between May 2009 and January 2016 were included in this retrospective study. The cohort of patients was divided into two separate groups for the training (99 patients) and validation (50 patients) in chronological order. Radiomics features were extracted from PET/CT images using Pyradiomics implemented in Python, and the XGBoost algorithm was used to build a prediction model. Conventional PET parameters, including standardized uptake value, metabolic tumor volume, and total lesion glycolysis, were also measured. The quality of the proposed model was appraised by means of receiver operating characteristics (ROC) and areas under the ROC curve (AUC). Results: The prediction model based on a twelve-feature-combined radiomics signature could stratify PDAC patients into grade 1 and grade 2/3 groups with AUC of 0.994 in the training set and 0.921 in the validation set. Conclusion: The model developed is capable of predicting pathological differentiation grade of PDAC based on preoperative 18F-FDG PET/CT radiomics features. [ABSTRACT FROM AUTHOR]

Background: The study aimed to establish a 68Ga-FAPI-04 kinetic model in hepatic lesions, to determine the potential role of kinetic parameters in the differentiation of hepatocellular carcinoma (HCC) from non-HCC lesions. Material and methods: Time activity curves (TACs) were extracted from seven HCC lesions and five non-HCC lesions obtained from 68Ga-FAPI-04 dynamic positron emission tomography (PET) scans of eight patients. Three kinetic models were applied to the TACs, using image-derived hepatic artery and/or portal vein as input functions. The maximum standardized uptake value (SUVmax) was taken for the lesions, the hepatic artery, and for the portal veins—the mean SUV for all healthy regions. The optimum model was chosen after applying the Schwartz information criteria to the TACs, differences in model parameters between HCC, non-HCC lesions, and healthy tissue were evaluated with the ANOVA test. Results: A reversible two-tissue compartment model using both the arterial as well as venous input function was most preferred and showed significant differences in the kinetic parameters VND, VT, and BPND between HCC, non-HCC lesions, and healthy regions (p < 0.01). Conclusion: Several model parameters derived from a two-tissue compartment kinetic model with two image-derived input function from vein and aorta and using SUVmax allow a differentiation between HCC and non-HCC lesions, obtained from dynamically performed PET scans using FAPI. [ABSTRACT FROM AUTHOR]

Purpose: 68Ga-FAPI-04 is a rapidly evolving PET tracer for whole-body imaging in a variety of cancers. We aimed to evaluate the diagnostic performance of 68Ga-FAPI-04 for detecting and characterizing hepatic nodules in patients with suspected carcinoma. Methods: Twenty-five patients showing suspicious hepatic lesions for malignancy underwent 68Ga-FAPI-04 PET. The maximum and mean standardised uptake values (SUVmax, SUVmean) were measured for all detected lesions and normal hepatic tissues, respectively. The target-to-background ratio (TBR) was calculated by dividing the lesion SUVmax with the SUVmean of non-tumour liver tissue. Lesion uptake value was correlated with the in vitro hepatic FAP expression determined by immunohistochemistry (IHC). Results: In total, 17 patients who underwent surgery or biopsy were recruited for the final analysis. A total of 28 intrahepatic malignant lesions were detected in 16 patients; the mean SUVmax was 8.36 ± 4.21 (range 2.21 to 15.86), and mean TBR was 13.15 ± 9.48 (range 2.79 to 38.12) in all detected lesions (n = 28). One benign patient showed negligible hepatic uptake (SUVmax = 0.47), whereas 75% of the primary intrahepatic hepatocellular carcinoma (HCC) lesions (n = 6) showed prominent FAP expression, 12.5% of the lesions (n = 1) showed moderate expression in stromal cells, and one showed negligible expression. Conclusions: 68Ga-FAPI-04 showed high sensitivity in detecting hepatic malignancies, particularly in poorly differentiated forms with concordantly elevated FAP expression. [ABSTRACT FROM AUTHOR]

Purpose The noninvasive imaging of bacterial infections is critical in order to reduce mortality and morbidity caused by these diseases. The recently reported 18 F-FDS ( 18 F-2-fluorodeoxy sorbitol) as a PET (positron emission tomography) tracer can be used to image Enterobacteriaceae-specific infections and provides a potential alternative to this problem compared with other probes for imaging infections. In this study, automatic synthesis, validation of 18 F-FDS and a first-in-human study were performed and discussed. Methods A multifunctional synthesis module was employed for the radiosynthesis of 18 F-FDG ( 18 F-2-fluorodeoxy glucose) and 18 F-FDS starting from 18 F ion using two-pot three-step fully automated reactions. The behavior of 18 F-FDS as an in vivo imaging probe for infections was evaluated in an Escherichia coli mouse infection model. The first detailed pharmacokinetic and biodistribution parameters were obtained from healthy human volunteers. Results The uptake of 18 F-FDS in an E. coli mouse-myositis infection model was easily differentiated from other organs and normal muscle. Intensive lesion uptake declined after antibiotic treatment. In the pilot human study, no adverse effects due to 18 F-FDS were observed up to 24 h post-injection. The radiotracer was rapidly cleared from the circulation and excreted mainly through the urinary system. Conclusion We conclude that 18 F-FDS PET holds great potential for appropriate and effective for the imaging of bacterial infections in vivo. These preliminary results indicate that further clinical studies are warranted. [ABSTRACT FROM AUTHOR]

Purpose: Clear cell renal cell carcinoma (ccRCC) highly expresses carbonic anhydrase IX (CAIX). The purpose of this study was to evaluate 68Ga-NY104, a small-molecule CAIX-targeting PET agent, in tumor models of ccRCC and patients diagnosed with confirmed, or suspicious, ccRCC. Methods: The in vivo and ex vivo biodistribution of 68Ga-NY104 was investigated in CAIX-positive OS-RC-2 xenograft-bearing models. The binding of the tracer was further validated using autoradiography for human ccRCC samples. In addition, three patients with confirmed or suspicious ccRCC were studied. Results: NY104 can be labeled with high radiochemical yield and purity. It quickly cleared through kidney with α-half-life of 0.15 h. Discernible uptake is noted in the heart, lung, liver, stomach, and kidney. The OS-RC-2 xenograft demonstrated intense uptake 5 min after injection and gradually increased until 3 h after injection with ID%/g of 29.29 ± 6.82. Significant binding was detected using autoradiography on sections of human ccRCC tumor. In the three patients studied, 68Ga-NY104 was well-tolerated and no adverse events were reported. Substantial accumulation was observed in both primary and metastatic lesions in patient 1 and 2 with SUVmax of 42.3. Uptake in the stomach, pancreas, intestine, and choroid plexus was noted. The lesion in third patient was correctly diagnosed as non-metastatic for negative 68Ga-NY104 uptake. Conclusion: 68Ga-NY104 can efficiently and specifically bind to CAIX. Given the pilot nature of our study, future clinical studies are warranted to evaluate 68Ga-NY104 for detection of CAIX-positive lesions in patients with ccRCC. Trial registration: The clinical evaluation part of this study was retrospectively registered at ClinicalTrial.gov (NCT05728515) as NYPILOT on 6 Feb, 2023. [ABSTRACT FROM AUTHOR]

Purpose: [(18)F]fluorodeoxysorbitol ([(18)F]FDS) is the first radiopharmaceutical specific for a category of bacteria and has the potential to specifically detect Enterobacteriaceae infections. The purpose of this study was to testify the safety and investigate the biodistribution and radiation dosimetry of [(18)F]FDS in healthy human bodies.Procedures: Six healthy subjects were intravenously injected with 320-520 MBq [(18)F]FDS. On each subject, 21 whole-body emission scans and a brain scan were conducted at settled time points within the next 4 h. Residence time for each source organ was determined by multi-exponential regression. Absorbed doses for target organs and effective dose were calculated via OLINDA/EXM.Results: No adverse events due to [(18)F]FDS injection were observed in the study. The tracer was cleared rapidly from the blood pool through the urinary system. A small portion was cleared into the gut through the hepatobiliary system. The effective dose (ED) was estimated to be 0.021 ± 0.001 mSv/MBq. The organ receiving the highest absorbed dose was the urinary bladder wall (0.25 ± 0.03 mSv/MBq).Conclusions: [(18)F]FDS is safe and well tolerated. The effective dose was comparable to that of other F-18 labeled radiotracers. [(18)F]FDS is suitable for human use from a radiation dosimetry perspective. [ABSTRACT FROM AUTHOR]

Background: Chronic alcohol consumption initially leads to asymptomatic left ventricular dysfunction, but can result in myocardial impairment and heart failure if ongoing. This study sought to characterize myocardial tissues and oxidative metabolism in asymptomatic subjects with chronic alcohol consumption by quantitative cardiovascular magnetic resonance (CMR) and 11C-acetate positron emission tomography (PET)/computed tomography (CT). Methods: Thirty-four male subjects (48.8 ± 9.1 years) with alcohol consumption > 28 g/day for > 10 years and 35 age-matched healthy male subjects (49.5 ± 9.7 years) underwent CMR and 11C-acetate PET/CT. Native and post T1 values and extracellular volume (ECV) from CMR and Kmono and K1 from PET imaging were measured. Quantitative measurements by CMR and PET imaging were compared between subjects with moderate to heavy alcohol consumption and healthy controls, and their correlations were also analyzed. Results: Compared to healthy controls, subjects with alcohol consumption showed significantly shorter native T1 (1133 ± 65 ms vs. 1186 ± 31 ms, p < 0.001) and post T1 (477 ± 42 ms vs. 501 ± 38 ms, p = 0.008) values, greater ECV (28.2 ± 2.2% vs. 26.9 ± 1.3%, p = 0.003), marginally lower Kmono (57.6 ± 12.1 min− 1 × 10− 3 vs. 63.0 ± 11.7 min− 1 × 10− 3, p = 0.055), and similar K1 (0.82 ± 0.13 min− 1 vs. 0.83 ± 0.15 min− 1, p = 0.548) after adjusting for confounding factors. There were no significant differences in CMR measurements and K1 between subjects with heavy and moderate alcohol consumption (all p > 0.05). In contrast, subjects with heavy alcohol consumption showed significantly lower Kmono values compared to those with moderate alcohol consumption (52.9 ± 12.1 min− 1 × 10− 3 vs. 63.7 ± 9.2 min− 1 × 10− 3, p = 0.012). Strong and moderate correlations were found between K1 and ECV in healthy controls (r = 0.689, p = 0.013) and subjects with moderate alcohol consumption (r = 0.518, p = 0.048), respectively. Conclusion: Asymptomatic men with heavy alcohol consumption have detectable structural and metabolic changes in myocardium on CMR and 11C-acetate PET/CT. Compared with quantitative CMR, 11C-acetate PET/CT imaging may be more sensitive for detecting differences in myocardial damage among subjects with moderate to heavy alcohol consumption. [ABSTRACT FROM AUTHOR]

Objective: Previously we observed that dual phase 11C-acetate positron emission tomography (AC-PET) could be employed for differential diagnosis of liver malignancies. In this study, we prospectively evaluated the effect of dual phase AC-PET on differential diagnosis of primary hepatic lesions of 1–3 cm in size. Methods: 33 patients having primary hepatic lesions with size of 1–3 cm in diameter undertook dual phase AC-PET scans. Procedure included an early upper-abdomen scan immediately after tracer injection and a conventional scan in 11–18 min. The standardized uptake value (SUV) was calculated for tumor (SUVT) and normal tissue (SUVB), from which 11C-acetate uptake ratio (as lesion against normal liver tissue, SUVT/SUVB) in early imaging (R1), conventional imaging (R2), and variance between R2 and R1 (ΔR) were derived. Diagnoses based on AC-PET data and histology were compared. Statistical analysis was performed with SPSS 19.0. Results: 20 patients were found to have HCC and 13 patients had benign tumors. Using ΔR>0 as criterion for malignancy, the accuracy and specificity were significantly increased comparing with conventional method. The area under ROC curve (AUC) for R1, R2, and ΔR were 0.417, 0.683 and 0.831 respectively. Differential diagnosis between well-differentiated HCCs and benign lesions of FNHs and hemangiomas achieved 100% correct. Strong positive correlation was also found between R1 and R2 in HCC (r2 = 0.55, P<0.001). Conclusions: Dual phase AC-PET scan is a useful procedure for differential diagnosis of well-differentiated hepatocellular carcinoma and benign lesions. The dynamic changes of 11C-acetate uptake in dual phase imaging provided key information for final diagnosis. [ABSTRACT FROM AUTHOR]

Brown adipose tissue (BAT) is emerging as a potential target for treating human obesity. It has been indicated that BAT is rich in innervations of sympathetic nerve control. Using (18)F-FDG microPET imaging, this study aims at evaluating how factors related to sympathetic activation/inhibition changed BAT metabolism of mice. BAT (18)F-FDG uptake were semiquantitatively evaluated in different groups of mice under temperature (cold or warm stimulus) or pharmacological interventions (norepinephrine, epinephrine, isoprenaline, or propranolol) and were compared with the corresponding controls. It was found that BAT activation can be stimulated by cold exposure (P = 1.96 x 10(-4)), norepinephrine (P = .002), or both (P = 2.19 x 10(-6)) within an hour before (18)F-FDG injection and can also be alleviated by warming up (P = .001) or propranolol lavage (P = .027). This preliminary study indicated that BAT function could be evaluated by (18)F-FDG PET imaging through short-term interventions, which paved the way for further investigation of the relationship between human obesity and BAT dysfunction. [ABSTRACT FROM AUTHOR]

Transplantation of bone marrow‐derived mesenchymal stem cells (BMSCs) is a potential therapy for cerebral ischemia. Although BMSCs‐induced angiogenesis is considered important for neurological functional recovery, the neurorestorative mechanisms are not fully understood. We examined whether BMSCs‐induced angiogenesis enhances cerebral tissue perfusion and creates a suitable microenvironment within the ischemic brain, which in turn accelerates endogenous neurogenesis and leads to improved functional recovery. Adult female rats subjected to 2 h middle cerebral artery occlusion (MCAO) were transplanted with a subpopulation of human BMSCs from male donors (Flk‐1+ hBMSCs) or saline into the ipsilateral brain parenchymal at 3 days after MCAO. Flk‐1+ hBMSCs‐treated rats exhibited significant behavioral recovery, beginning at 2 weeks after cerebral ischemia compared with controls. Moreover, rats treated with Flk‐1+ hBMSCs showed increased glucose metabolic activity and reduced infarct volume. Flk‐1+ hBMSCs treatment significantly increased the expression of vascular endothelial growth factor and brain‐derived neurotrophic factor, promoted angiogenesis, and facilitated cerebral blood flow in the ischemic boundary zone. Further, Flk‐1+ hBMSCs treatment enhanced proliferation of neural stem/progenitor cells (NSPCs) in the subventricular zone and subgranular zone of the hippocampus. Finally, more NSPCs migrated toward the ischemic lesion and differentiated to mature neurons or glial cells with less apoptosis in Flk‐1+ hBMSCs‐treated rats. These data indicate that angiogenesis induced by Flk‐1+ hBMSCs promotes endogenous neurogenesis, which may cause functional recovery after cerebral ischemia. [ABSTRACT FROM AUTHOR]

Background: PoleStar m660 is a newly developed clinical PET/CT system with time-of-flight (TOF) capability. The aim of this study is to characterize the performance of the new system. Spatial resolution, sensitivity, scatter fraction, and noise equivalent count rate (NECR) were measured on the scanner according to the NEMA NU 2-2012 protocol. The timing resolution was measured using a rotating line source that orbited around the center of field of view (CFOV) at a radius of 20 cm. The image quality phantom was also imaged to quantify the percent contrast, percent background variability, and residual error. The impacts of data acquisition time and bed overlap on the PET image quality were also evaluated using phantom and patient studies.Results: The transverse (axial) spatial resolutions were 3.59 mm (3.67), 4.08 mm (4.65), and 5.32 mm (6.48) full width at half maximum (FWHM) at 1 cm, 10 cm, and 20 cm, respectively, off the CFOV. The measured sensitivity was 10.7 cps/kBq at the CFOV and 10.4 cps/kBq at 10 cm off the CFOV. The peak NECR was 216.7 kcps at an activity concentration of 29.1 kBq/ml, and the scatter fraction was 38.2%. An average of 435 ps FWHM timing resolution was measured. For the image quality phantom, the contrast recovery ratios ranged from 33.9 to 76.4%, while the background variability ranged from 4.7 to 2.0%. In the preliminary clinical study, no noticeable difference in the image quality was observed when the scan time for the whole body and brain was reduced to 1 min/bed and 3 min, respectively. The tested 21% bed overlap showed no significant difference in the image quality compared with the default 38% bed overlap setting.Conclusions: The physical performances of the PoleStar m660 PET/CT system showed good sensitivity, count rate performance, and timing resolution. The improved performance could help to reduce the acquisition time and bed overlap in the clinical application without detectable compromise in the image quality. [ABSTRACT FROM AUTHOR]