Selective neurodegeneration of the hippocampus caused by chronic cerebral hypoperfusion: F-18 FDG PET study in rats.

BACKGROUND: Chronic cerebral hypoperfusion (CCH) is known to induce Alzheimer's disease (AD) pathology, but its mechanism remains unclear. The purpose of this study was to identify the cerebral regions that are affected by CCH, and to evaluate the development of AD pathology in a rat model of CCH. METHODS: A rat model of CCH was established by bilaterally ligating the common carotid arteries in adult male rats (CCH group). The identical operations were performed on sham rats without arteries ligation (control group). Regional cerebral glucose metabolism was evaluated at 1 and 3 months after bilateral CCA ligation using positron emission tomography with F-18 fluorodeoxyglucose. The expression levels of amyloid ß40 (Aß40), amyloid ß42 (Aß42), and hyperphosphorylated tau were evaluated using western blots at 3 months after the ligation. Cognitive function was evaluated using the Y-maze test at 3 months after the ligation. RESULTS: At 1 month after the ligation, cerebral glucose metabolism in the entorhinal, frontal association, motor, and somatosensory cortices were significantly decreased in the CCH group compared with those in the control group. At 3 months after the ligation, cerebral glucose metabolism was normalized in all regions except for the anterodorsal hippocampus, which was significantly decreased compared with that of the control group. The expression of Aß42 and the Aß42/40 ratio were significantly higher in the CCH group than those in the control group. The phosphorylated-tau levels of the hippocampus in the CCH group were significantly lower than those in the control group. Cognitive function was more impaired in the CCH group than that in the control group. CONCLUSION: Our findings suggest that CCH causes selective neurodegeneration of the anterodorsal hippocampus, which may be a trigger point for the development of AD pathology.

Neoadjuvant immunotherapy with nivolumab and ipilimumab induces major pathological responses in patients with head and neck squamous cell carcinoma.

Surgery for locoregionally advanced head and neck squamous cell carcinoma (HNSCC) results in 30‒50% five-year overall survival. In IMCISION (NCT03003637), a non-randomized phase Ib/IIa trial, 32 HNSCC patients are treated with 2 doses (in weeks 1 and 3) of immune checkpoint blockade (ICB) using nivolumab (NIVO MONO, n = 6, phase Ib arm A) or nivolumab plus a single dose of ipilimumab (COMBO, n = 26, 6 in phase Ib arm B, and 20 in phase IIa) prior to surgery. Primary endpoints are feasibility to resect no later than week 6 (phase Ib) and primary tumor pathological response (phase IIa). Surgery is not delayed or suspended for any patient in phase Ib, meeting the primary endpoint. Grade 3‒4 immune-related adverse events are seen in 2 of 6 (33%) NIVO MONO and 10 of 26 (38%) total COMBO patients. Pathological response, defined as the %-change in primary tumor viable tumor cell percentage from baseline biopsy to on-treatment resection, is evaluable in 17/20 phase IIa patients and 29/32 total trial patients (6/6 NIVO MONO, 23/26 COMBO). We observe a major pathological response (MPR, 90‒100% response) in 35% of patients after COMBO ICB, both in phase IIa (6/17) and in the whole trial (8/23), meeting the phase IIa primary endpoint threshold of 10%. NIVO MONO's MPR rate is 17% (1/6). None of the MPR patients develop recurrent HSNCC during 24.0 months median postsurgical follow-up. FDG-PET-based total lesion glycolysis identifies MPR patients prior to surgery. A baseline AID/APOBEC-associated mutational profile and an on-treatment decrease in hypoxia RNA signature are observed in MPR patients. Our data indicate that neoadjuvant COMBO ICB is feasible and encouragingly efficacious in HNSCC.

GLUT1, GLUT3 Expression and 18FDG-PET/CT in Human Malignant Melanoma: What Relationship Exists? New Insights and Perspectives.

BACKGROUND: Malignant melanoma is the most aggressive of skin cancers and the 19th most common cancer worldwide, with an estimated age-standardized incidence rate of 2.8-3.1 per 100,000; although there have been clear advances in therapeutic treatment, the prognosis of MM patients with Breslow thickness greater than 1 mm is still quite poor today. The study of how melanoma cells manage to survive and proliferate by consuming glucose has been partially addressed in the literature, but some rather interesting results are starting to be present. METHODS: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and a search of PubMed and Web of Sciences (WoS) databases was performed until 27 September 2021 using the terms: glucose transporter 1 and 3 and GLUT1/3 in combination with each of the following: melanoma, neoplasm and immunohistochemistry. RESULTS: In total, 46 records were initially identified in the literature search, of which six were duplicates. After screening for eligibility and inclusion criteria, 16 publications were ultimately included. CONCLUSIONS: the results discussed regarding the role and expression of GLUT are still far from definitive, but further steps toward understanding and stopping this mechanism have, at least in part, been taken. New studies and new discoveries should lead to further clarification of some aspects since the various mechanisms of glucose uptake by neoplastic cells are not limited to the transporters of the GLUT family alone.

The Value of 18F-FDG PET/CT in Evaluating Disease Severity and Prognosis in Idiopathic Pulmonary Fibrosis Patients.

BACKGROUND: Several parameters are useful for assessing disease severity in idiopathic pulmonary fibrosis (IPF); however, the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is not well-defined. We aimed to evaluate the value of 18F-FDG PET/CT for assessing disease severity and prognosis in IPF patients. METHODS: Clinical data of 89 IPF patients (mean age: 68.1 years, male: 94%) who underwent 18F-FDG PET/CT for evaluation of lung nodules or cancer staging were retrospectively reviewed. Mean and maximal standardized uptake values (SUVmean, SUVmax, respectively) were measured in the fibrotic area. Adjusted SUV, including SUV ratio (SUVR, defined as SUVmax-to-liver SUVmean ratio), tissue fraction-corrected SUVmean (SUVmeanTF), and SUVR (SUVRTF), and tissue-to-blood ratio (SUVmax/SUVmean venous; TBRblood) were obtained. Death was defined as the primary outcome, and associations between other clinical parameters (lung function, exercise capacity, C-reactive protein [CRP] level) were also investigated. RESULTS: All SUV parameters were inversely correlated with the forced vital capacity, diffusing capacity for carbon monoxide, and positively correlated with CRP level and the gender-age-physiology index. The SUVmean, SUVmax, and SUVmeanTF were associated with changes in lung function at six months. The SUVR (hazard ratio [HR], 1.738; 95% confidence interval [CI], 1.011-2.991), SUVRTF (HR, 1.441; 95% CI, 1.000-2.098), and TBRblood (HR, 1.377; 95% CI, 1.038-1.827) were significant predictors for mortality in patients with IPF in the univariate analysis, but not in the multivariate analysis. CONCLUSION: 18F-FDG PET/CT may provide additional information on the disease severity and prognosis in IPF patients, and the SUVR may be superior to other SUV parameters.

Relationship between Cerebrospinal Fluid Matrix Metalloproteinases Levels and Brain Amyloid Deposition in Mild Cognitive Impairment.

This study aimed to explore whether cerebrospinal fluid (CSF) levels of matrix metalloproteinases (MMPs), and their inhibitors (TIMPs) were associated with brain amyloid deposition, cortical glucose metabolism, and white matter lesions (WMLs) in individuals with amnestic mild cognitive impairment (MCI). A total of 33 individuals with amnestic MCI (mean age, 75.6 years) underwent 11C-Pittsburgh compound B positron emission tomography (PiB-PET), 18F-fluorodeoxyglucose positron emission tomography, magnetic resonance imaging or computed tomography, and CSF analysis. PET uptake of the frontal and temporoparietal lobes and posterior cingulate gyrus was assessed using the cerebellar cortex as the reference region. WMLs were assessed by the Fazekas scale. CSF levels of MMPs and TIMPs were measured with bead-based multiplex assays. After adjusting for covariates, multiple linear regression analysis showed that CSF levels of MMP-2 were negatively correlated with global PiB uptake (p = 0.035), especially in the parietotemporal lobe and posterior cingulate gyrus (p = 0.016 and p = 0.041, respectively). Moreover, CSF levels of MMP-7 were positively correlated with the severity of WMLs (p = 0.033). CSF levels of MMP-2 and MMP-7 are associated with brain amyloid deposition and severity of WMLs, respectively. These findings provide valuable insights into the role of MMPs in amyloid ß catabolism and blood-brain barrier integration at the MCI stage.

CT texture analysis of tonsil cancer: Discrimination from normal palatine tonsils.

The purposes of the study were to determine whether there are differences in texture analysis parameters between tonsil cancers and normal tonsils, and to correlate texture analysis with 18F-FDG PET/CT to investigate the relationship between texture analysis and metabolic parameters. Sixty-four patients with squamous cell carcinoma of the palatine tonsil were included. A ROI was drawn, including all slices, to involve the entire tumor. The contralateral normal tonsil was used for comparison with the tumors. Texture analysis parameters, mean, standard deviation (SD), entropy, mean positive pixels, skewness, and kurtosis were obtained using commercially available software. Parameters were compared between the tumor and the normal palatine tonsils. Comparisons were also performed among early tonsil cancer, advanced tonsil cancer, and normal tonsils. An ROC curve analysis was performed to assess discrimination of tumor from normal tonsils. Correlation between texture analysis and 18F-FDG PET/CT was performed. Compared to normal tonsils, the tumors showed a significantly lower mean, higher SD, higher entropy, lower skewness, and higher kurtosis on most filters (p<0.001). On comparisons among normal tonsils, early cancers, and advanced tonsil cancers, SD and entropy showed significantly higher values on all filters (p<0.001) between early cancers and normal tonsils. The AUC from the ROC analysis was 0.91, obtained from the entropy. A mild correlation was shown between texture parameters and metabolic parameters. The texture analysis parameters, especially entropy, showed significant differences in contrast-enhanced CT results between tumor and normal tonsils, and between early tonsil cancers and normal tonsils. Texture analysis can be useful as an adjunctive tool for the diagnosis of tonsil cancers.

Specific features to differentiate Giant cell arteritis aortitis from aortic atheroma using FDG-PET/CT.

Aortic wall 18F-fluorodeoxyglucose (FDG)-uptake does not allow differentiation of aortitis from atheroma, which is problematic in clinical practice for diagnosing large vessel vasculitis giant-cell arteritis (GCA) in elderly patients. The purpose of this study was to compare the FDG uptake characteristics of GCA aortitis and aortic atheroma using positron emission tomography/FDG computed tomography (FDG-PET/CT). This study compared FDG aortic uptake between patients with GCA aortitis and patients with aortic atheroma; previously defined by contrast enhanced CT. Visual grading according to standardized FDG-PET/CT interpretation criteria and semi-quantitative analyses (maximum standardized uptake value (SUVmax), delta SUV (∆SUV), target to background ratios (TBR)) of FDG aortic uptake were conducted. The aorta was divided into 5 segments for analysis. 29 GCA aortitis and 66 aortic atheroma patients were included. A grade 3 FDG uptake of the aortic wall was identified for 23 (79.3%) GCA aortitis patients and none in the atheroma patient group (p < 0.0001); grade 2 FDG uptake was as common in both populations. Of the 29 aortitis patients, FDG uptake of all 5 aortic segments was positive for 21 of them (72.4%, p < 0.0001). FDG uptake of the supra-aortic trunk was identified for 24 aortitis (82.8%) and no atheromatous cases (p < 0.0001). All semi-quantitative analyses of FDG aortic wall uptake (SUVmax, ∆SUV and TBRs) were significantly higher in the aortitis group. ∆SUV was the feature with the largest differential between aortitis and aortic atheroma. In this study, GCA aortitis could be distinguished from an aortic atheroma by the presence of an aortic wall FDG uptake grade 3, an FDG uptake of the 5 aortic segments, and FDG uptake of the peripheral arteries.

Differences among [18F]FDG PET-derived parameters in lung cancer produced by three software packages.

Investigation of differences in derived [18F]FDG PET metabolic and volumetric parameters among three different software programs in lung cancer. A retrospective analysis was performed on a group of 98 lung cancer patients who underwent a baseline [18F]FDG PET/CT study. To assess appropriate delineation methods, the NEMA phantom study was first performed using the following software: Philips EBW (Extended Brilliance Workstation), MIM Software and Rover. Based on this study, the best cut-off methods (dependent on tumour size) were selected, extracted and applied for lung cancer delineation. Several semiquantitative [18F]FDG parameters (SUVmax, SUVmean, TLG and MTV) were assessed and compared among the three software programs. The parameters were assessed based on body weight (BW), lean body mass (LBM) and Bq/mL. Statistically significant differences were found in SUVmean (LBM) between MIM Software and Rover (4.62 ± 2.15 vs 4.84 ± 1.20; p < 0.005), in SUVmean (Bq/mL) between Rover and Philips EBW (21,852.30 ± 21,821.23 vs 19,274.81 ± 13,340.28; p < 0.005) and Rover and MIM Software (21,852.30 ± 21,821.23 vs 19,399.40 ± 10,051.30; p < 0.005), and in MTV between MIM Software and Philips EBW (19.87 ± 25.83 vs 78.82 ± 228.00; p = 0.0489). This study showed statistically significant differences in the estimation of semiquantitative parameters using three independent image analysis tools. These findings are important for performing further diagnostic and treatment procedures in lung cancer patients.

Peptide VSAK maintains tissue glucose uptake and attenuates pro-inflammatory responses caused by LPS in an experimental model of the systemic inflammatory response syndrome: a PET study.

The present investigation using Positron Emission Tomography shows how peptide VSAK can reduce the detrimental effects produced by lipopolysaccharides in Dutch dwarf rabbits, used to develop the Systemic Inflammatory Response Syndrome (SIRS). Animals concomitantly treated with lipopolysaccharides (LPS) and peptide VSAK show important protection in the loss of radiolabeled-glucose uptake observed in diverse organs when animals are exclusively treated with LPS. Treatment with peptide VSAK prevented the onset of changes in serum levels of glucose and insulin associated with the establishment of SIRS and the insulin resistance-like syndrome. Treatment with peptide VSAK also allowed an important attenuation in the circulating levels of pro-inflammatory molecules in LPS-treated animals. As a whole, our data suggest that peptide VSAK might be considered as a candidate in the development of new therapeutic possibilities focused on mitigating the harmful effects produced by lipopolysaccharides during the course of SIRS.

A molecular pathology, neurobiology, biochemical, genetic and neuroimaging study of progressive apraxia of speech.

Progressive apraxia of speech is a neurodegenerative syndrome affecting spoken communication. Molecular pathology, biochemistry, genetics, and longitudinal imaging were investigated in 32 autopsy-confirmed patients with progressive apraxia of speech who were followed over 10 years. Corticobasal degeneration and progressive supranuclear palsy (4R-tauopathies) were the most common underlying pathologies. Perceptually distinct speech characteristics, combined with age-at-onset, predicted specific 4R-tauopathy; phonetic subtype and younger age predicted corticobasal degeneration, and prosodic subtype and older age predicted progressive supranuclear palsy. Phonetic and prosodic subtypes showed differing relationships within the cortico-striato-pallido-nigro-luysial network. Biochemical analysis revealed no distinct differences in aggregated 4R-tau while tau H1 haplotype frequency (69%) was lower compared to 1000+ autopsy-confirmed 4R-tauopathies. Corticobasal degeneration patients had faster rates of decline, greater cortical degeneration, and shorter illness duration than progressive supranuclear palsy. These findings help define the pathobiology of progressive apraxia of speech and may have consequences for development of 4R-tau targeting treatment.

18F-FDG-PET/CT Whole-Body Imaging Lung Tumor Diagnostic Model: An Ensemble E-ResNet-NRC with Divided Sample Space.

Under the background of 18F-FDG-PET/CT multimodal whole-body imaging for lung tumor diagnosis, for the problems of network degradation and high dimension features during convolutional neural network (CNN) training, beginning with the perspective of dividing sample space, an E-ResNet-NRC (ensemble ResNet nonnegative representation classifier) model is proposed in this paper. The model includes the following steps: (1) Parameters of a pretrained ResNet model are initialized using transfer learning. (2) Samples are divided into three different sample spaces (CT, PET, and PET/CT) based on the differences in multimodal medical images PET/CT, and ROI of the lesion was extracted. (3) The ResNet neural network was used to extract ROI features and obtain feature vectors. (4) Individual classifier ResNet-NRC was constructed with nonnegative representation NRC at a fully connected layer. (5) Ensemble classifier E-ResNet-NRC was constructed using the "relative majority voting method." Finally, two network models, AlexNet and ResNet-50, and three classification algorithms, nearest neighbor classification algorithm (NNC), softmax, and nonnegative representation classification algorithm (NRC), were combined to compare with the E-ResNet-NRC model in this paper. The experimental results show that the overall classification performance of the Ensemble E-ResNet-NRC model is better than the individual ResNet-NRC, and specificity and sensitivity are more higher; the E-ResNet-NRC has better robustness and generalization ability.

Design, synthesis, and evaluation of positron emission tomography/fluorescence dual imaging probes for targeting facilitated glucose transporter 1 (GLUT1).

Increased energy metabolism followed by enhanced glucose consumption is a hallmark of cancer. Most cancer cells show overexpression of facilitated hexose transporter GLUT1, including breast cancer. GLUT1 is the main transporter for 2-deoxy-2-[18F]fluoro-d-glucose (2-[18F]FDG), the gold standard of positron emission tomography (PET) imaging in oncology. The present study's goal was to develop novel glucose-based dual imaging probes for their use in tandem PET and fluorescence (Fl) imaging. A glucosamine scaffold tagged with a fluorophore and an 18F-label should confer selectivity to GLUT1. Out of five different compounds, 2-deoxy-2-((7-sulfonylfluoro-2,1,3-benzoxadiazol-4-yl)amino)-d-glucose (2-FBDG) possessed favorable fluorescent properties and a similar potency as 2-deoxy-2-((7-nitro-2,1,3-benzoxadiazol-4-yl)amino)-d-glucose (2-NBDG) in competing for GLUT1 transport against 2-[18F]FDG in breast cancer cells. Radiolabeling with 18F was achieved through the synthesis of prosthetic group 7-fluoro-2,1,3-benzoxadiazole-4-sulfonyl [18F]fluoride ([18F]FBDF) followed by the reaction with glucosamine. The radiotracer was finally analyzed in vivo in a breast cancer xenograft model and compared to 2-[18F]FDG. Despite favourable in vitro fluorescence imaging properties, 2-[18F]FBDG was found to lack metabolic stability in vivo, resulting in radiodefluorination. Glucose-based 2-[18F]FBDG represents a novel dual-probe for GLUT1 imaging using FI and PET with the potential for further structural optimization for improved metabolic stability in vivo.

The Future of Cancer Diagnosis, Treatment and Surveillance: A Systemic Review on Immunotherapy and Immuno-PET Radiotracers.

Immunotherapy is an effective therapeutic option for several cancers. In the last years, the introduction of checkpoint inhibitors (ICIs) has shifted the therapeutic landscape in oncology and improved patient prognosis in a variety of neoplastic diseases. However, to date, the selection of the best patients eligible for these therapies, as well as the response assessment is still challenging. Patients are mainly stratified using an immunohistochemical analysis of the expression of antigens on biopsy specimens, such as PD-L1 and PD-1, on tumor cells, on peritumoral immune cells and/or in the tumor microenvironment (TME). Recently, the use and development of imaging biomarkers able to assess in-vivo cancer-related processes are becoming more important. Today, positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is used routinely to evaluate tumor metabolism, and also to predict and monitor response to immunotherapy. Although highly sensitive, FDG-PET in general is rather unspecific. Novel radiopharmaceuticals (immuno-PET radiotracers), able to identify specific immune system targets, are under investigation in pre-clinical and clinical settings to better highlight all the mechanisms involved in immunotherapy. In this review, we will provide an overview of the main new immuno-PET radiotracers in development. We will also review the main players (immune cells, tumor cells and molecular targets) involved in immunotherapy. Furthermore, we report current applications and the evidence of using [18F]FDG PET in immunotherapy, including the use of artificial intelligence (AI).

Comparison of the [18F]-FDG and [18F]-FLT PET Tracers in the Evaluation of the Preclinical Proton Therapy Response in Hepatocellular Carcinoma.

PURPOSE: The main objective of the present study was to compare the 2-deoxy-2-[18F]fluoro-D-glucose ([18F]-FDG) and 3'-[18F]fluoro-3'-deoxythymidine ([18F]-FLT) PET imaging biomarkers for the longitudinal follow-up of small animal proton therapy studies in the context of hepatocellular carcinoma (HCC). PROCEDURES: SK-HEP-1 cells were injected into NMRI nude mice to mimic human HCC. The behavior of [18F]-FDG and [18F]-FLT tumor uptake was evaluated after proton therapy procedures. The proton single-fraction doses were 5, 10, and 20 Gy, with a dose rate of 10 Gy/min. The experimental protocol consisted of 8 groups of 10 mice, each group experiencing a particular dose/radiotracer condition. A reference PET exam was performed on each mouse the day before the irradiation procedure, followed by PET exams every 3 days up to 16 days after irradiation. RESULTS: [18F]-FDG uptake showed a linear dose-dependent increase in the first days after treatment (37%, p < 0.05), while [18F]-FLT uptake decreased in a dose-dependent manner (e.g., 21% for 5 Gy compared to 10 Gy, p = 1.1e-2). At the later time point, [18F]-FDG normalized activity showed an 85% decrease (p < 0.01) for both 10 and 20 Gy doses and no variation for 5 Gy. Conversely, a significant 61% (p = 0.002) increase was observed for [18F]-FLT normalized activity at 5 Gy and no variation for higher doses. CONCLUSION: We showed that the use of the [18F]-FDG and [18F]-FLT radiolabeled molecules can provide useful and complementary information for longitudinal follow-up of small animal proton therapy studies in the context of HCC. [18F]-FDG PET imaging enables a treatment monitoring several days/weeks postirradiation. On the other hand, [18F]-FLT could represent a good candidate to monitor the treatment few days postirradiation, in the context of hypo-fractioned and close irradiation planning. This opens new perspectives in terms of treatment efficacy verification depending on the irradiation scheme.

Rectal dose-sparing effect with bioabsorbable spacer placement in carbon ion radiotherapy for sacral chordoma: dosimetric comparison of a simulation study.

It is difficult to treat patients with an inoperable sarcoma adjacent to the gastrointestinal (GI) tract using carbon ion radiotherapy (C-ion RT), owing to the possible development of serious GI toxicities. In such cases, spacer placement may be useful in physically separating the tumor and the GI tract. We aimed to evaluate the usefulness of spacer placement by conducting a simulation study of dosimetric comparison in a patient with sacral chordoma adjacent to the rectum treated with C-ion RT. The sacral chordoma was located in the third to fourth sacral spinal segments, in extensive contact with and compressing the rectum. Conventional C-ion RT was not indicated because the rectal dose would exceed the tolerance dose. Because we chose spacer placement surgery to physically separate the tumor and the rectum before C-ion RT, bioabsorbable spacer sheets were inserted by open surgery. After spacer placement, 67.2 Gy [relative biological effectiveness (RBE)] of C-ion RT was administered. The thickness of the spacer was stable at 13-14 mm during C-ion RT. Comparing the dose-volume histogram (DVH) parameters, Dmax for the rectum was reduced from 67 Gy (RBE) in the no spacer plan (simulation plan) to 45 Gy (RBE) in the spacer placement plan (actual plan) when a prescribed dose was administered to the tumor. Spacer placement was advantageous for irradiating the tumor and the rectum, demonstrated using the DVH parameter analysis.

Additional Value of Integrated 18F-FDG PET/MRI for Evaluating Biliary Tract Cancer: Comparison with Contrast-Enhanced CT.

OBJECTIVE: To evaluate the value of 18F-fluorodeoxyglucose PET/MRI added to contrast-enhanced CT (CECT) in initial staging, assessment of resectability, and postoperative follow-up of biliary tract cancer. MATERIALS AND METHODS: This retrospective study included 100 patients (initial workup [n = 65] and postoperative follow-up [n = 35]) who had undergone PET/MRI and CECT for bile duct or gallbladder lesions between January 2013 and March 2020. Two radiologists independently reviewed the CECT imaging set and CECT plus PET/MRI set to determine the likelihood of malignancy, local and overall resectability, and distant metastasis in the initial workup group, and local recurrence and distant metastasis in the follow-up group. Diagnostic performances of the two imaging sets were compared using clinical-surgical-pathologic findings as standards of reference. RESULTS: The diagnostic performance of CECT significantly improved after the addition of PET/MRI for liver metastasis (area under the receiver operating characteristic curve [Az]: 0.77 vs. 0.91 [p = 0.027] for reviewer 1; 0.76 vs. 0.92 [p = 0.021] for reviewer 2), lymph node metastasis (0.73 vs. 0.92 [p = 0.004]; 0.81 vs. 0.92 [p = 0.023]), and overall resectability (0.79 vs. 0.92 [p = 0.007]; 0.82 vs. 0.94 [p = 0.021]) in the initial workup group. In the follow-up group, the diagnostic performance of CECT plus PET/MRI was significantly higher than that of CECT imaging for local recurrence (0.81 vs. 1.00 [p = 0.029]; 0.82 vs. 0.94 [p = 0.045]). CONCLUSION: PET/MRI may add value to CECT in patients with biliary tract cancer both in the initial workup for staging and determination of overall resectability and in follow-up for local recurrence.

Association between PD-L1 expression and 18F-FDG uptake in ovarian cancer.

OBJECTIVE: Immunotherapy for programmed cell death 1 (PD-1) and its ligand, PD-L1, has been considered an effective treatment for ovarian cancer. 18F-labeled fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is a widely used noninvasive imaging tool for diagnosing several cancers. In this study, we investigated the association between PD-L1 expression and the maximum standardized uptake value (SUVmax) using 18F-FDG PET/CT. METHODS: We retrospectively analyzed clinical data of patients with ovarian cancer who underwent 18F-FDG PET/CT. Patients were categorized into two groups according to PD-L1 expression results. The relationship between clinicopathological characteristics of patients with ovarian cancer and PD-L1 expression was examined. RESULTS: SUVmax was significantly higher in PD-L1-positive tumors than in PD-L1-negative tumors (16.1 ± 5.2 and 12.7 ± 7.0, respectively; p = 0.026). There were no significant differences in age, histologic type, and tumor grade between the PD-L1-negative and PD-L1-positive groups. The receiver operating characteristic curve analysis demonstrated that the highest accuracy (61.8%) for predicting PD-L1 expression was obtained with an SUVmax cutoff value of 10.5. CONCLUSION: There was a significant correlation between 18F-FDG uptake and PD-L1 expression, suggesting a role of 18F-FDG PET/CT in selecting ovarian cancer candidates for anti-PD-L1 antibody therapy.

Digital PET/CT allows for shorter acquisition protocols or reduced radiopharmaceutical dose in [18F]-FDG PET/CT.

PURPOSE: To establish the feasibility of shorter acquisition times (and by analogy, applied activity) on tumour detection and lesion contrast in digital PET/CT. METHODS: Twenty-one randomly selected patients who underwent oncological [18F]-FDG PET/CT on a digital PET/CT were retrospectively evaluated. Scan data were anonymously obtained and reconstructed in list-mode acquisition for a standard 2 min/bed position (bp), 1 min/bp and 30 s/bp (100%, 50% and 25% time or applied activity, respectively). Scans were randomized and read by two nuclear medicine physicians in a consensus read. Readers were blind to clinical details. Scans were evaluated for the number of pathological lesions detected. Measured uptake for lesions was evaluated by maximum and mean standardized uptake value (SUVmax and SUVmean, respectively) and tumour-to-backround ratio (TBR) were compared. Agreement between the three acquisitions was compared by Krippendorf's alpha. RESULTS: Overall n = 100 lesions were identified in the 2 min and 1 min/bp acquisitions and n = 98 lesions in the 30 s/bp acquisitions. Agreement between the three acquisitions with respect to lesion number and tumour-to-background ratio showed almost perfect agreement (K's α = 0.999). SUVmax, SUVmean and TBR likewise showed > 98% agreement, with longer acquisitions being associated with slightly higher mean TBR (2 min/bp 7.94 ± 4.41 versus 30 s/bp 7.84 ± 4.22, p < 0.05). CONCLUSION: Shorter acquisition times have traditionally been associated with reduced lesion detectability or the requirement for larger amounts of radiotracer activity. These data confirm that this is not the case for new-generation digital PET scanners, where the known higher sensitivity results in clinically adequate images for shorter acquisitions. Only a small variation in the semi-quantitative parameters SUVmax, SUVmean and TBR was seen, confirming that either reduction of acquisition time or (by analogy) applied activity can be reduced as much as 75% in digital PET/CT without apparent clinical detriment.

Prediction of local recurrence and distant metastasis using radiomics analysis of pretreatment nasopharyngeal [18F]FDG PET/CT images.

OBJECTIVES: To develop a radiomics signature to predict locoregional recurrence (LR) and distant metastasis (DM), as extracted from pretreatment 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography/X-ray computed tomography (PET/CT) images in locally advanced nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Eighty-five patients with Stage III-IVB NPC underwent pretreatment [18F]FDG PET/CT scans and received radiotherapy or chemoradiotherapy. 53 of them achieved disease control, and 32 of them failed after treatment (15: LR, 17: DM). A total of 114 radiomic features were extracted from PET/CT images. For univariate analysis, Wilcoxon test and Chi-square test were used to compare median values of features between different treatment outcomes and predict the risk of treatment failure, respectively. For multivariate analysis, all features were grouped into clusters based on Pearson correlation using hierarchical clustering, and the representative feature of each cluster was chosen by the Relief algorithm. Then sequential floating forward selection (SFFS) coupled with a support vector machine (SVM) classifier were used to derive the optimized feature set in terms of the area under receiver operating characteristic (ROC) curve (AUC). The performance of the model was evaluated by leave-one-out-cross-validation, fivefold cross-validation, tenfold cross-validation. RESULTS: Twenty features had significant differences between disease control and treatment failure. NPC patients with values of Compactness1, Compactness2, Coarseness_NGTDM or SGE_GLGLM above the median as well as patients with values of Irregularity, RLN_GLRLM or GLV_GLSZM below the median, showed a significant (p < 0.05) higher risk of treatment failure (about 50% vs. 25%). The derived radiomics signature consisted of 5 features with the highest AUC value of 0.8290 (sensitivity: 0.8438, specificity: 0.7736) using leave-one-out-cross-validation. CONCLUSION: Locoregional recurrence (LR) and DM of locally advanced NPC can be predicted using radiomics analysis of pretreatment [18F]FDG PET/CT. The SFFS feature selection coupled with SVM classifier can derive the optimized feature set with correspondingly highest AUC value for pretreatment prediction of LR and/or DM of NPC.

Synthesis and Characterization of [18F]JNJ-46356479 as the First 18F-Labeled PET Imaging Ligand for Metabotropic Glutamate Receptor 2.

PURPOSE: Metabotropic glutamate receptor 2 (mGluR2) has been implicated in various psychiatric and neurological disorders, such as schizophrenia and Alzheimer's disease. We have previously developed [11C]7 as a PET radioligand for imaging mGluR2. Herein, [18F]JNJ-46356479 ([18F]8) was synthesized and characterized as the first 18F-labeled mGluR2 imaging ligand to enhance diagnostic approaches for mGluR2-related disorders. PROCEDURES: JNJ-46356479 (8) was radiolabeled via the copper (I)-mediated radiofluorination of organoborane 9. In vivo PET imaging experiments with [18F]8 were conducted first in C57BL/6 J mice and Sprague-Dawley rats to obtain whole body biodistribution and brain uptake profile. Subsequent PET studies were done in a cynomolgus monkey (Macaca fascicularis) to investigate the uptake of [18F]8 in the brain, its metabolic stability, as well as pharmacokinetic properties. RESULTS: JNJ-46356479 (8) exhibited excellent selectivity against other mGluRs. In vivo PET imaging studies showed reversible and specific binding characteristic of [18F]8 in rodents. In the non-human primate, [18F]8 displayed good in vivo metabolic stability, excellent brain permeability, fast and reversible kinetics with moderate heterogeneity across brain regions. Pre-treatment studies with compound 7 revealed time-dependent decrease of [18F]8 accumulation in mGluR2 rich regions based on SUV values with the highest decrease in the nucleus accumbens (18.7 ± 5.9%) followed by the cerebellum (18.0 ± 7.9%), the parietal cortex (16.9 ± 7.8%), and the hippocampus (16.8 ± 6.9%), similar to results obtained in the rat studies. However, the volume of distribution (VT) results derived from 2T4k model showed enhanced VT from a blocking study with compound 7. This is probably because of the potentiating effect of compound 7 as an mGluR2 PAM as well as related non-specific binding in the tissue data. CONCLUSIONS: [18F]8 readily crosses the blood-brain barrier and demonstrates fast and reversible kinetics both in rodents and in a non-human primate. Further investigation of [18F]8 on its binding specificity would warrant translational study in human.