Exploring ASL perfusion MRI as a substitutive modality for 18F-FDG PET in determining the laterality of mesial temporal lobe epilepsy.

OBJECTIVE: The aim of this investigation was to determine whether a correlation could be discerned between perfusion acquired through ASL MRI and metabolic data acquired via 18F-fluorodeoxyglucose (18F-FDG) PET in mesial temporal lobe epilepsy (mTLE). METHODS: ASL MRI and 18F-FDG PET data were gathered from 22 mTLE patients. Relative cerebral blood flow (rCBF) asymmetry index (AIs) were measured using ASL MRI, and standardized uptake value ratio (SUVr) maps were obtained from 18F-FDG PET, focusing on bilateral vascular territories and key bitemporal lobe structures (amygdala, hippocampus, and parahippocampus). Intra-group comparisons were carried out to detect hypoperfusion and hypometabolism between the left and right brain hemispheres for both rCBF and SUVr in right and left mTLE. Correlations between the two AIs computed for each modality were examined. RESULTS: Significant correlations were observed between rCBF and SUVr AIs in the middle temporal gyrus, superior temporal gyrus, and hippocampus. Significant correlations were also found in vascular territories of the distal posterior, intermediate anterior, intermediate middle, proximal anterior, and proximal middle cerebral arteries. Intra-group comparisons unveiled significant differences in rCBF and SUVr between the left and right brain hemispheres for right mTLE, while hypoperfusion and hypometabolism were infrequently observed in any intracranial region for left mTLE. CONCLUSION: The study's findings suggest promising concordance between hypometabolism estimated by 18F-FDG PET and hypoperfusion determined by ASL perfusion MRI. This raises the possibility that, with prospective technical enhancements, ASL perfusion MRI could be considered an alternative modality to 18F-FDG PET in the future.

Reflecting on the utility of standardized uptake values on 18F-FDG PET in nasopharyngeal carcinoma.

BACKGROUND: To rethink the clinical significance of standardized uptake values (SUVs) of nasopharyngeal carcinoma (NPC) on 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET). METHODS: We retrospectively reviewed 369 NPC patients who underwent pretreatment 18F-FDG PET. The predictive value of the SUVmax of the primary tumor (SUVmax-t) and regional lymph nodes (SUVmax-n) was evaluated using probability density functions. Receiver operating characteristic curves were used to determine optimal cutoffs for the SUVmax-n/SUVmax-t ratio (NTR). Kaplan-Meier and Cox regression analyses were used to assess survival. RESULTS: The optimal SUVmax-t and SUVmax-n cutoffs were 7.5 and 6.9, respectively. High SUVmax-t and SUVmax-n were related to local and regional recurrence, respectively. Patients with low SUVmax had better 3-year overall survival (OS). To avoid cross-sensitization of cutoff points, we stratified patients with high SUVmax into the low and high NTR groups. The 3-year distant metastasis-free survival (DMFS; 92.3 vs. 80.6%, P = 0.009), progression-free survival (PFS; 84.0 vs. 67.7%, P = 0.011), and OS (95.9 vs. 89.2%, P = 0.002) significantly differed between the high vs. low NTR groups for patients with high SUVmax. Multivariable analysis showed that NTR was an independent prognostic factor for DMFS (hazard ratio [HR]: 2.037, 95% CI: 1.039-3.992, P = 0.038), PFS (HR: 1.636, 95% CI: 1.021-2.621, P = 0.041), and OS (HR: 2.543, 95% CI: 1.214-5.325, P = 0.013). CONCLUSION: High SUVmax was associated with NPC recurrence. NTR is a potential prognosticator for DMFS, suggesting that heterogeneity in the pretreatment 18F-FDG uptake between the primary tumor and lymph nodes is associated with high invasion and metastatic potential.

Validation of a dedicated positron emission tomography scanner for imaging of the distal limb of standing horses.

A positron emission tomography (PET) scanner, with an openable ring of detectors, was specifically designed to image the distal limb of standing horses. The goals of this prospective, preclinical, experimental, methods comparison study were to validate the safety of the scanner, assess image quality, and optimize scanning protocols. Six research horses were imaged three times (twice standing, once anesthetized) and six horses in active race training were imaged once under standing sedation. Multiple scans of both front fetlocks were obtained with different scan durations and axial fields of view. A total of 94 fetlock scans were attempted and 90 provided images of diagnostic value. Radiotracer uptake was the main factor affecting image quality, while motion did not represent a major issue. Scan duration and field of view also affected image quality. Eight specific lesions were identified on PET images from anesthetized horses and were all also independently recognized on the PET images obtained on standing horses. Maximal standardized uptake values (SUVmax) had good repeatability for the assessment of specific lesions among different scans. Three feet and six carpi were also successfully imaged. This study validated the safety and practicality of a PET scanner specifically designed to image the distal limb in standing horses. Proper preparation of horses, similar to bone scintigraphy, is important for image quality. A 4-min scan with 12 cm field of view was considered optimal for clinical fetlock imaging. Evaluation of a larger clinical population is the next step for further assessment of the clinical utility of PET imaging in horses.

The Warburg effect: persistence of stem-cell metabolism in cancers as a failure of differentiation.

Background: Two recent observations regarding the Warburg effect are that (i) the metabolism of stem cells is constitutive (aerobic) glycolysis while normal cellular differentiation involves a transition to oxidative phosphorylation and (ii) the degree of glucose uptake of a malignancy as imaged by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is associated with histologic measures of tumor differentiation. Combining these observations, we hypothesized that the high levels of glucose uptake observed in poorly differentiated cancers may reflect persistence of the glycolytic metabolism of stem cells in malignant cells that fail to fully differentiate. Patients and methods: Tumor glucose uptake was measured by FDG-PET in 552 patients with histologically diverse cancers. We used normal mixture modeling to explore FDG-PET standardized uptake value (SUV) distributions and tested for associations between glucose uptake and histological differentiation, risk of lymph node metastasis, and survival. Using RNA-seq data, we carried out pathway and transcription factor analyses to compare tumors with high and low levels of glucose uptake. Results: We found that well-differentiated tumors had low FDG uptake, while moderately and poorly differentiated tumors had higher uptake. The distribution of SUV for each histology was bimodal, with a low peak around SUV 2-5 and a high peak at SUV 8-14. The cancers in the two modes were clinically distinct in terms of the risk of nodal metastases and death. Carbohydrate metabolism and the pentose-related pathway were elevated in the poorly differentiated/high SUV clusters. Embryonic stem cell-related signatures were activated in poorly differentiated/high SUV clusters. Conclusions: Our findings support the hypothesis that the biological basis for the Warburg effect is a persistence of stem cell metabolism (i.e. aerobic glycolysis) in cancers as a failure to transition from glycolysis-utilizing undifferentiated cells to oxidative phosphorylation-utilizing differentiated cells. We found that cancers cluster along the differentiation pathway into two groups, utilizing either glycolysis or oxidative phosphorylation. Our results have implications for multiple areas of clinical oncology.

Higher fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) uptake in tuberculous compared to bacterial spondylodiscitis.

BACKGROUND: Tuberculous spondylodiscitis can be difficult to diagnose because of its nonspecific symptoms and the similarities with non-tubercular forms of spinal infection. Fluorine-18-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG PET-CT) is increasingly used for the diagnosis and monitoring of tubercular diseases. METHODS: Retrospective, case-control study comparing tuberculous spondylodiscitis with biopsy-confirmed pyogenic spondylodiscitis in the period 2010-2012. RESULTS: Ten cases of tuberculous spondylodiscitis and 20 controls were included. Compared to pyogenic, tuberculous spondylodiscitis was more frequent in younger patients (P = 0.01) and was more often associated with thoraco-lumbar tract lesions (P = 0.01) and multiple vertebral involvement (P = 0.01). Significantly higher maximum standardized uptake values (SUV) at FDG-PET were displayed by tuberculous spondylodiscitis compared to controls (12.4 vs. 7.3, P = 0.003). SUV levels above 8 showed the highest value of specificity (0.80). Mean SUV reduction of 48% was detected for tuberculous spondylodiscitis at 1-month follow-up. CONCLUSIONS: Higher SUV levels at FDG-PET were detected in tuberculous compared with pyogenic spondylodiscitis. PET-CT use appeared useful in the disease follow-up after treatment initiation.

PET/CT standardized uptake value and EGFR expression predicts treatment failure in nasopharyngeal carcinoma.

OBJECTIVE: This study inventively combines epidermal growth factor receptor (EGFR) expression of the primary lesion and standardized uptake value (SUV) of positron emission tomography and computed tomography (PET/CT) to predict the prognosis of nasopharyngeal carcinoma (NPC). This study aimed to evaluate the predictive efficacy of maximum standard uptake value (SUVmax) and EGFR for treatment failure in patients with NPC. METHODS: This retrospective study reviewed the results of EGFR expression and pretreatment 18F-FDG PET/CT of 313 patients with NPC. Time-dependent receiver operator characteristics was used for analyzing results and selecting the optimal cutoff values. Cox regression was used to screen out multiple risk factors. Cumulative survival rate was calculated by Kaplan-Meier. RESULTS: The selected cutoff value of SUVmax-T was 8.5. The patients were categorized into four groups according to EGFR expression and SUVmax-T. There were significant differences in the 3-year local recurrence-free survival (LRFS) (p = 0.0083), locoregional relapse-free survival (LRRFS) (p = 0.0077), distant metastasis-free survival (DMFS) (p = 0.013), and progression-free survival (PFS) (p = 0.0018) among the four groups. Patients in the EGFR-positive and SUVmax-T > 8.5 group had the worst survival, while patients in the EGFR-negative and SUVmax-T ≤ 8.5 group had the best prognosis. Subsequently, patients with only positive EGFR expression or high SUVmax-T were classified as the middle-risk group. There were also a significant difference in 3-year overall survival among the three risk groups (p = 0.034). SUVmax-T was associated with regional recurrence-free survival and LRRFS in multivariate analysis, whereas EGFR was an independent prognostic factor for LRRFS, DMFS, and PFS. CONCLUSION: The combination of SUVmax-T and EGFR expression can refine prognosis and indicate clinical therapy.

Investigation of tumor assessment between two PET systems using various indices: comparison between PET/CT and PET/MRI systems.

This study aimed to determine the comparability of tumor-uptake indices of 18F-FDG in positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance imaging (PET/MRI). 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) PET/CT and PET/MRI were performed on 55 patients with confirmed primary malignancies. PET/CT preceded PET/MRI in all examinations. Accumulation of 18F-FDG in lesions and normal organs (brain, liver) was measured. Maximum and peak standardized uptake values (SUVs; SUVmax and SUVpeak, respectively), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) with margin thresholds of SUV of 50% (MTV50%; TLG50%, respectively) were measured as indices for comparison of measurements in tumors. Comparative indices with tumor SUVmax and liver ratio (TLRmax), brain ratio (TBRmax) were calculated. These indices were compared between PET/CT and PET/MRI examinations. The data measured using PET/CT and PET/MRI showed significant correlations for all tumor indices. The correlation was strongest for SUVpeak (r = 0.933), followed by TBRmax (r = 0.929); and the index ratio of (PET/CT)/(PET/MRI) data was close to 1.0 for TLRmax (1.00 ± 0.22) and TBRmax (1.01 ± 0.21), followed by MTV50% (0.82 ± 0.33) and TLG50% (1.18 ± 0.45). The values of all indices showed strong correlations between PET/CT and PET/MRI examinations. Among them, TLRmax, TBRmax, MTV50%, and TLG50% showed a close value and may be useful for comparison of tumor evaluation between two PET systems.

Diagnostic value of hybrid FDG-PET/MR imaging of chronic osteomyelitis.

BACKGROUND: Magnetic resonance imaging (MRI) and 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) Positron Emission Tomography, paired with Computed Tomography (PET/CT) are commonly used modalities in the complicated diagnostic work-up of osteomyelitis. PET/MRI is a relatively novel hybrid modality with suggested applications in bone infection imaging, based on expert opinion and previous qualitative research. 18F-FDG PET/MRI has the advantages of reduced radiation dose, more soft tissue information, and is deemed more valuable for surgical planning compared to 18F-FDG PET/CT. The goal of this study is to quantitatively assess the diagnostic value of hybrid 18F-FDG PET/MRI for chronic osteomyelitis. METHODS: A retrospective analysis was performed by a nuclear medicine physician and radiologist on 36 patients with 18F-FDG PET/MRI scans for suspected osteomyelitis. Sensitivity, specificity, and accuracy were determined with the clinical assessment by the orthopaedic surgeon (based on subsequent intraoperative microbiology or long-term follow-up) as the ground truth. Standardized uptake values (SUV) were measured and analysed by means of receiver operating characteristics (ROC). RESULTS: This first study to quantitatively report the diagnostic value of 18F-FDG PET/MRI yielded a sensitivity, specificity, and accuracy of 78%, 100%, and 86% respectively. Area under the ROC curve was .736, .755, and .769 for the SUVmax, target to background ratio, and SUVmax_ratio respectively. These results are in the same range and not statistically different compared to diagnostic value for 18F-FDG PET/CT imaging of osteomyelitis in literature. CONCLUSIONS: Based on the aforementioned advantages of 18F-FDG PET/MRI and the diagnostic value reported here, the authors propose 18F-FDG PET/MRI as an alternative to 18F-FDG PET/CT in osteomyelitis diagnosis, if available.

Ex vivo γH2AX assay for tumor radiosensitivity in primary prostate cancer patients and correlation with clinical parameters.

BACKROUND: Accurate surrogate parameters for radio resistance are warranted for individualized radiotherapy (RT) concepts in prostate cancer (PCa). The purpose of this study was to assess intertumoral heterogeneity in terms of radio resistance using an ex-vivo γH2AX assay after irradiation of prostate biopsy cores and to investigate its correlation with clinical features of respective patients as well as imaging and genomic features of tumor areas. METHODS: Twenty one patients with histologically-proven PCa and pre-therapeutic multiparametric resonance imaging and prostate-specific membrane antigen positron emission tomography were included in the study. Biopsy cores were collected from 26 PCa foci. Residual γH2AX foci were counted 24 h after ex-vivo irradiation (with 0 and 4 Gy) of biopsy specimen and served as a surrogate for radio resistance. Clinical, genomic (next generation sequencing) and imaging features were collected and their association with the radio resistance was studied. RESULTS: In total 18 PCa lesions from 16 patients were included in the final analysis. The median γH2AX foci value per PCa lesion was 3.12. According to this, the patients were divided into two groups (radio sensitive vs. radio resistant) with significant differences in foci number (p < 0.0001). The patients in the radio sensitive group had significantly higher prostate specific antigen serum concentration (p = 0.015), tumor areas in the radio sensitive group had higher SUV (standardized uptake values in PSMA PET)-max and -mean values (p = 0.0037, p = 0.028) and lower ADC (apparent diffusion coefficient-mean values, p = 0.049). All later parameters had significant (p < 0.05) correlations in Pearson's test. One patient in the radio sensitive group displayed a previously not reported loss of function frameshift mutation in the NBN gene (c.654_658delAAAAC) that introduces a premature termination codon and results in a truncated protein. CONCLUSION: In this pilot study, significant differences in intertumoral radio resistance were observed and clinical as well as imaging parameters may be applied for their prediction. After further prospective validation in larger patient cohorts these finding may lead to individual RT dose prescription for PCa patients in the future.

F-FDG18PET/CT incidental detection of tumor-to-tumor metastasis in patients investigated for squamous cell lung cancer.

Tumor-to-tumor metastasis (TTM) is a well-known entity, although this is still an extremely rare phenomenon. The lung cancers are considered the most frequent metastatic donors while kidney cancers are the most common recipient. The finding of TTM is often incidental during a biopsy of metastases or on surgical specimens but never suspected on radiological assessment of tumor extension. The finding of an unexpected region of Fluorodeoxyglucose (FDG) uptake can occur when performing whole body Positron Emission Tomography/computed tomography (PET/CT) scan and potentially raises the possibility of a second primary tumor. However, PET/CT scan incidental detection of tumor-to-tumor metastasis has never been reported in English literature. We report here a case of clear cell renal carcinoma, receptor of metastases originating from an oligometastatic squamous cell lung cancer detected on the PET/CT scan performed as part of the extension workup. Morphological and immunohistochemical analysis of a percutaneous biopsy of the renal mass were consistent with the diagnosis of a metastasis of lung cancer into renal cell carcinoma. This is the first case of oligometastatic lung cancer with the occurrence of TTM suspected in PET/CT scan. Although this is a rare setting, it should be considered in daily practice, as it could potentially modify the oncological management offered to the patients.

Schwannoma: A rare cause of false-positive 68Ga-PSMA PET/CT uptake in the evaluation of metastatic prostate cancer.

PSMA expression occurs in epithelial cells in both normal and hyperplastic prostates. In adenocarcinoma, it is present in greater intensity, especially in the more aggressive ones. This made it possible to develop diagnostic tools with greater specificity for detecting prostate cancer metastases like the 68Ga-PSMA PET/CT. Several benign neoplasms with increased marker uptake have been described in the literature. Such false-positives are usually associated with soft tissue injuries, abnormal vascular proliferation, neurogenic injuries, thymomas and adenomas. In the present work we present a case report that exemplifies the above.

New criteria of resectability for pancreatic cancer: A position paper by the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS).

The symposium "New criteria of resectability for pancreatic cancer" was held during the 33nd meeting of the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) in 2021 to discuss the potential modifications that could be made in the current resectability classification. The meeting focused on setting the foundation for developing a new prognosis-based resectability classification that is based on the tumor biology and the response to neoadjuvant treatment (NAT). The symposium included selected experts from Western and Eastern high-volume centers who have discussed their concept of resectability status through published literature. During the symposium, presenters reported new resectability classifications from their respective institutions based on tumor biology, conditional status, pathology, and genetics, in addition to anatomical tumor involvement. Interestingly, experts from all the centers reached the agreement that anatomy alone is insufficient to define resectability in the current era of effective NAT. On behalf of the JSHBPS, we would like to summarize the content of the conference in this position paper. We also invite global experts as internal reviewers of this paper for intercontinental cooperation in creating an up-to-date, prognosis-based resectability classification that reflects the trends of contemporary clinical practice.

Toward Reliable Uptake Metrics in Large Vessel Vasculitis Studies.

The aim of this study is to investigate the influence of sex, age, fat mass, fasting blood glucose level (FBGL), and estimated glomerular filtration rate (eGFR) on blood pool activity in patients with large vessel vasculitis (LVV). Blood pool activity was measured in the superior caval vein using mean, maximum, and peak standardized uptake values corrected for body weight (SUVs) and lean body mass (SULs) in 41 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scans of LVV patients. Sex influence on the blood pool activity was assessed with t-tests, while linear correlation analyses were used for age, fat mass, FBGL, and eGFR. Significantly higher SUVs were found in women compared with men, whereas SULs were similar between sexes. In addition, higher fat mass was associated with increased SUVs (r = 0.56 to 0.65; all p < 0.001) in the blood pool, but no correlations were found between SULs and fat mass (r = -0.25 to -0.15; all p > 0.05). Lower eGFR was associated with a higher FDG blood pool activity for all uptake values. In FDG-PET/CT studies with LVV patients, we recommend using SUL over SUV, while caution is advised in interpreting SUV and SUL measures when patients have impaired kidney function.

Implications of Standardized Uptake Values of Oral Squamous Cell Carcinoma in PET-CT on Prognosis, Tumor Characteristics and Mitochondrial DNA Heteroplasmy.

Under aerobic conditions, some cancers switch to glycolysis to cover their energy requirements. Taking advantage of this process, functional imaging techniques such as PET-CT can be used to detect and assess tumorous tissues. The aim of this study was to investigate standardized uptake values and mitochondrial DNA mutations in oral squamous cell carcinoma. A cohort of 57 patients underwent 18[F]FDG-PET-CT and standardized uptake values were collected. In 15 patients, data on mitochondrial DNA mutations of the tumor were available. Kaplan-Meier curves were calculated, and correlation analyses as well as univariate Cox proportional hazard models were performed. Using ROC analysis to determine a statistical threshold for SUVmax in PET investigations, a cut-off value was determined at 9.765 MB/mL. Survival analysis for SUVmax in these groups showed a Hazard Ratio of 4 (95% CI 1.7-9) in the high SUVmax group with 5-year survival rates of 23.5% (p = 0.00042). For SUVmax and clinicopathological tumor features, significant correlations were found. A tendency towards higher mtDNA heteroplasmy levels in high SUVmax groups could be observed. We were able to confirm the prognostic value of SUVmax in OSCC, showing higher survival rates at lower SUVmax levels. Correlations between SUVmax and distinct tumor characteristics were highly significant, providing evidence that SUVmax may act as a reliable diagnostic parameter. Correlation analysis of mtDNA mutations suggests an influence on metabolic activity in OSCC.

Variation of Tumor Volume During Moderate Hypo-Fractionated Stereotactic Body Radiation Therapy for Lung Cancer.

Aim To investigate the variation of tumor volume during moderate hypo-fractionated stereotactic body radiation therapy (SBRT). Patients and Methods Twenty patients, who received SBRT at our institution, were included in the analysis. A prescribed dose was 56 Gy at iso-center in seven fractions. Tumor volumes before and during SBRT were calculated. In order to investigate factors affecting the variation of tumor volume in RT 2 (after first irradiation) and RT 7 (after last irradiation), various parameters were verified by the Mann-Whitney U test. Results With regard to the low maximum standardized uptake values (SUVmax) group, transient increase of tumor volume was found in RT 2, and tumor volume reduction was hardly found in RT 7. With regard to the high SUVmax group, a transient increase was not found, and a definite reduction was found in the treatment course. Conclusion Accurate prediction of tumor volume variation is required for more accurate treatment, such as adaptive radiation therapy.

Evaluation of the Accuracy of Standardized Uptake Values of 18F-fluorodeoxyglucose in Lung Lesions Based on Phantom Studies.

The aim of the study was to estimate the accuracy of standardized uptake values of 18F-fluorodeoxyglucose (18F-FDG) in lung lesions during positron emission tomography combined with computed tomography (PET/CT) imaging, based on phantom studies performed for different PET/CT scanners. MATERIALS AND METHODS: The analysis of the PET/CT with 18F-FDG data was performed for 86 patients newly diagnosed with the lung lesions: malignant tumors (n=37), benign tumors and inflammatory diseases (n=49). The criteria for inclusion in the study were developed considering the recommendations of the Fleischner Society (2017). The characteristics of the lesions on CT met the following requirements: a round shape or close to it; total size of 8 to 30 mm; solid or subsolid structure (with the exception of lesion with ground-glass opacity); a solid part size of ≥8 mm. All the patients had no signs of pleurisy, lymphadenopathy, or cancer history. PET/CT imaging with 18F-FDG was performed with three scanners: Discovery 690 (General Electric, USA), Biograph mCT 128 (Siemens, Germany), and Biograph mCT 40 (Siemens); the preparation of patients prior to the scan was standardized. To determine the reference accumulation of a radiopharmaceutical in the pathological lesion, four scans of a specialized NEMA IEC PET Body Phantom Set (USA) were performed for each scanner. For each unit, the recovery coefficients (RCs) of radioactivity, maximum and recovered (corrected) standardized uptake values (SUVs) were determined. Statistical relationship between the size of lesions, SUVmax and SUVcorrect was evaluated. Data processing was performed using MedCalc v. 19.2.0 software. RESULTS: During the phantom study, the underestimation of the radioactivity was determined in the spheres with the diameters of 10 and 13 mm, overestimation was observed in the sphere with the diameter of 28 mm. Both underestimation and overestimation of radioactivity were determined for the spheres with a diameter of 17 and 22 mm.SUVmax differed from the reference values for 85 patients (98.8%). The underestimation of these values was found for 63 patients (73.2%) due to the partial volume effect. The greatest underestimation was observed for the patients with 8 mm diameter lesions. Depending on the scanner, the underestimation of the SUVmax in these patients reached up to 54-73%. For 9 patients (25%) with malignant tumors of 9-12 mm, the utility of RC made it possible to avoid false negative results. For the lesions with a diameter of 30 mm, an overestimation of SUVmax up to 22% was determined due to the negative influence of the reconstruction algorithms. CONCLUSION: The use of RC eliminates the influence of the partial volume effect and reconstruction methods on the accuracy of estimating the SUVmax in lung lesions, which ensures reproducibility, increase in the information content of the method, as well as the comparability of the results of PET/CT with 18F-FDG obtained on the different models of PET/CT units with different technological characteristics.

PET/CT Imaging of 89Zr-N-sucDf-Pembrolizumab in Healthy Cynomolgus Monkeys.

PURPOSE: Programmed cell death-1 receptor (PD-1) and its ligand (PD-L1) are the targets for immunotherapy in many cancer types. Although PD-1 blockade has therapeutic effects, the efficacy differs between patients. Factors contributing to this variability are PD-L1 expression levels and immune cells present in tumors. However, it is not well understood how PD-1 expression in the tumor microenvironment impacts immunotherapy response. Thus, imaging of PD-1-expressing immune cells is of interest. This study aims to evaluate the biodistribution of Zirconium-89 (89Zr)-labeled pembrolizumab, a humanized IgG4 kappa monoclonal antibody targeting PD-1, in healthy cynomolgus monkeys as a translational model of tracking PD-1-positive immune cells. PROCEDURES: Pembrolizumab was conjugated with the tetrafluorophenol-N-succinyl desferal-Fe(III) ester (TFP-N-sucDf) and subsequently radiolabeled with 89Zr. Four cynomolgus monkeys with no previous exposure to humanized monoclonal antibodies received tracer only or tracer co-injected with pembrolizumab intravenously over 5 min. Thereafter, a static whole-body positron emission tomography (PET) scan was acquired with 10 min per bed position on days 0, 2, 5, and 7. Image-derived standardized uptake values (SUVmean) were quantified by region of interest (ROI) analysis. RESULTS: 89Zr-N-sucDf-pembrolizumab was synthesized with high radiochemical purity (> 99 %) and acceptable molar activity (> 7 MBq/nmol). In animals dosed with tracer only, 89Zr-N-sucDf-pembrolizumab distribution in lymphoid tissues such as mesenteric lymph nodes, spleen, and tonsils increased over time. Except for the liver, low radiotracer distribution was observed in all non-lymphoid tissue including the lung, muscle, brain, heart, and kidney. When a large excess of pembrolizumab was co-administered with a radiotracer, accumulation in the lymph nodes, spleen, and tonsils was reduced, suggestive of target-mediated accumulation. CONCLUSIONS: 89Zr-N-sucDf-pembrolizumab shows preferential uptake in the lymphoid tissues including the lymph nodes, spleen, and tonsils. 89Zr-N-sucDf-pembrolizumab may be useful in tracking the distribution of a subset of immune cells in non-human primates and humans. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02760225.

Downregulated GPR30 expression in the epileptogenic foci of female patients with focal cortical dysplasia type IIb and tuberous sclerosis complex is correlated with 18 F-FDG PET-CT values.

Focal cortical dysplasia type IIb (FCDIIb) and tuberous sclerosis complex (TSC) are typical causes of developmental delay and refractory epilepsy. G-protein-coupled receptor 30 (GPR30) is a specific estrogen receptor that is critical in neurodevelopment, neuroinflammation, and neuronal excitability, suggesting that it plays a potential role in the epilepsy of patients with FCDIIb and TSC. Therefore, we investigated the role of GPR30 in patients with FCDIIb and TSC. We found that the expression of GPR30 and its downstream protein kinase A (PKA) pathway were decreased and negatively correlated with seizure frequency in female patients with FCDIIb and TSC, but not in male patients. GPR30 was widely distributed in neurons, astrocytes, and microglia, and its downregulation was especially notable in microglia. The GPR30 agonist G-1 increased the expression of PKA and p-PKA in cultured cortical neurons, and the GPR30 antagonist G-15 exhibited the opposite effects of G-1. The NF-κB signaling pathway was also activated in the specimens of female patients with FCDIIb and TSC, and was regulated by G-1 and G-15 in cultured cortical neurons. We also found that GPR30 regulated cortical neuronal excitability by altering the frequency of spontaneous excitatory postsynaptic currents and the expression of NR2A/B. Further, the relationship between GPR30 and glycometabolism was evaluated by analyzing the correlations between GPR30 and 18 F-FDG PET-CT values (standardized uptake values, SUVs). Positive correlations between GPR30 and SUVs were found in female patients, but not in male patients. Intriguingly, GPR30 expression and SUVs were significantly decreased in the epileptogenic tubers of female TSC patients, and ROC curves indicated that SUVs could predict the localization of epileptogenic tubers. Taken together, our results suggest a potential protective effect of GPR30 in the epileptogenesis of female patients with FCDIIb and TSC.

Ferumoxytol Does Not Impact Standardized Uptake Values on PET/MR Scans.

PURPOSE: Tumor response assessments on positron emission tomography (PET)/magnetic resonance imaging (MRI) scans require correct quantification of radiotracer uptake in tumors and normal organs. Historically, MRI scans have been enhanced with gadolinium (Gd)-based contrast agents, which are now controversial due to brain deposition. Recently, ferumoxytol nanoparticles have been identified as an alternative to Gd-based contrast agents because they provide strong tissue enhancement on MR images but are not deposited in the brain. However, it is not known if the strong T1- and T2-contrast obtained with iron oxide nanoparticles such as ferumoxytol could affect MR-based attenuation correction of PET data. The purpose of our study was to investigate if ferumoxytol administration prior to a 2-deoxy-2-[18F]fluoro-D-glucose [18F]FDG PET/MR scan would change standardized uptake values (SUV) of normal organs. PROCEDURES: Thirty pediatric patients (6-18 years) with malignant tumors underwent [18F]FDG-PET/MR scans (dose 3 MBq/kg). Fifteen patients received an intravenous ferumoxytol injection (5 mg Fe/kg) prior to the [18F]FDG-PET/MR scans (group 1). Fifteen additional age- and sex-matched patients received unenhanced [18F]FDG-PET/MR scans (group 2). For attenuation correction of PET data, we used a Dixon-based gradient echo sequence (TR 4.2 ms, TE 1.1, 2.3 ms, FA 5), which accounted for soft tissue, lung, fat, and background air. We used a mixed linear effects model to compare the tissue MRI enhancement, quantified as the signal-to-noise ratio (SNR), as well as tissue radiotracer signal, quantified as SUVmean and SUVmax, between group 1 and group 2. Alpha was assumed at 0.05. RESULTS: The MRI enhancement of the blood and solid extra-cerebral organs, quantified as SNR, was significantly higher on ferumoxytol-enhanced MRI scans compared to unenhanced scans (p < 0.001). However, SUVmean and SUVmax values, corrected based on the patients' body weight or body surface area, were not significantly different between the two groups (p > 0.05). CONCLUSION: Ferumoxytol administration prior to a [18F]FDG PET/MR scan did not change standardized uptake values (SUV) of solid extra-cerebral organs. This is important, because it allows injection of ferumoxytol contrast prior to a PET/MRI procedure and, thereby, significantly accelerates image acquisition times.

F-18 fluorodeoxyglucose uptake in lymph nodes and sonographic features on endobronchial ultrasonography predict lymph node metastasis in lung cancer patients.

BACKGROUND: Sonographic findings of lymph nodes on endobronchial ultrasonography (EBUS) images have been reported to be useful to predict lymph node metastasis (LNM) in lung cancer patients. F-18 fluorodeoxyglucose (FDG) uptake in lymph nodes was also found to be useful. In this study, we aimed to clarify whether a combination of sonographic features and maximum standardized uptake values of lymph nodes (LN-SUVmax) is useful for predicting LNM in lung cancer patients. METHODS: From January 2014 to December 2019, a total of 147 lymph nodes from 104 patients with lung cancer, who underwent preoperative EBUS and FDG-positron emission tomography (PET)/computed tomography (CT) followed by surgery were retrospectively assesses. The characteristics of the patients, LN-SUVmax, and sonographic findings of lymph nodes were reviewed. Predictive factors associated with LNM were identified using the logistic regression model. RESULTS: The average size of the lymph nodes was 8.55 (range, 3-22) mm and the average LN-SUVmax was 5.36 (range, 1.79-31.19). The prevalence of nodal metastasis was 26/147 (17.4%), including 22 in mediastinal lymph nodes and 4 in hilar lymph nodes. Multivariate analysis demonstrated four independent predictive factors for LNM; size, round or oval shape, absence of a central hilar structure, and LN-SUVmax. The optimal cutoff value for lymph node size and LN-SUVmax were 10 mm and 6.00, respectively. By combinating of the two modalities, we obtained the results with sensitivity of 76.9%, specificity of 95.1% and accuracy of 93.2%. CONCLUSIONS: A combination of sonographic findings and LN-SUVmax showed a higher diagnostic rate of LNM than either modality alone in lung cancer patients.