Assessment of Myocardial 18F-FDG Uptake at PET/CT in Asymptomatic SARS-CoV-2-vaccinated and Nonvaccinated Patients.

Background Patients who developed myocarditis following SARS-CoV-2 vaccination show abnormalities on cardiac MRI. However, whether myocardial changes occur in asymptomatic individuals following vaccination is not well established. Purpose To assess myocardial 18Fluorine-fluorodeoxyglucose (18F-FDG) uptake on PET/CT in asymptomatic SARS-CoV-2 vaccinated patients compared to nonvaccinated patients. Materials and Methods This retrospective study included patients who underwent 18F-FDG PET/CT for indications unrelated to myocarditis during the period before (11/1/2020 - 2/16/2021) and after (2/17/20121 - 3/31/2022) SARS-CoV-2 vaccines were available. Myocardial and axillary FDG uptake were quantitatively assessed using maximum standardized uptake value (SUVmax). SUVmax values in all patients and in patients stratified by sex (male/female), age (<40, 41-60, >60 years), and time interval between vaccination and PET/CT were compared using Mann-Whitney U test or Kruskal-Wallis test with post ad -hoc Dwass, Steel, Critchlow-Fligner multiple comparison analysis. Results The study included 303 nonvaccinated patients (mean age, 52.9 years ± 14.9 [SD]; 157 females) and 700 vaccinated patients (mean age, 56.8 years ± 13.7 [SD]; 344 females). Vaccinated patients had overall higher myocardial FDG uptake compared to nonvaccinated patients (median SUVmax, 4.8 [IQR: 3.0-8.5] vs median SUVmax, 3.3 [IQR: 2.5-6.2]; P < .0001). Myocardial SUVmax was higher in vaccinated patients regardless of sex (median range, 4.7-4.9 [IQR: 2.9-8.6]) or patient age (median range, 4.7-5.6 [IQR: 2.9-8.6]) compared to corresponding nonvaccinated groups (sex median range, 3.2-3.9 [IQR: 2.4-7.2]; age median range, 3.3-3.3 [IQR: 2.3-6.1]; P range, <.001-.015). Furthermore, increased myocardial FDG uptake was observed in patients imaged 1-30, 31-60, 61-120, and 121-180 days after their second vaccination (median SUVmax range, 4.6-5.1 [IQR: 2.9-8.6]) and increased ipsilateral axillary uptake was observed in patients imaged 1-30, 31-60, 61-120 days after their 2nd vaccination (median SUVmax range, 1.5-2.0 [IQR: 1.2-3.4]) compared to the nonvaccinated patients (P range, <.001-<.001). Conclusion Compared to nonvaccinated patients, asymptomatic patients who received their 2nd vaccination 1-180 days prior to imaging showed increased myocardial FDG uptake on PET/CT. See also the editorial by Bluemke in this issue.

Impact of patient characteristic factors on the dynamics of liver glucose metabolism: Evaluation of multiparametric imaging with dynamic whole-body 18 F-fluorodeoxyglucose-positron emission tomography.

AIMS: To assess the impact of various patient characteristics on the dynamics of liver glucose metabolism using automated multiparametric imaging with whole-body dynamic 18 F-fluorodeoxyglucose (FDG)-positron emission tomography (PET). MATERIALS AND METHODS: We retrospectively enrolled 540 patients who underwent whole-body dynamic FDG-PET. Three quantitative indices representing hepatic glucose metabolism [mean standardized uptake value normalized by lean body mass (SULmean), metabolic glucose rate (kinetic index) and distribution volume (DV)] were measured from multiparametric PET images produced automatically based on the Patlak plot model. Patient characteristics including age, sex, body mass index, fasting time, blood glucose level, and the presence of diabetes mellitus (DM) or hepatic steatosis (HS) were collected. We examined the correlations between the characteristic factors and three quantitative indices using multiple regression analysis. RESULTS: The success rate of kinetic analysis using multiparametric PET imaging was 93.3% (504/540). Hepatic SULmean was significantly correlated with age (p < .001), sex (p < .001) and blood glucose level (p = .002). DV was significantly correlated with age (p = .033), sex (p < .001), body mass index (p = .002), fasting time (p = .043) and the presence of HS (p = .002). The kinetic index was significantly correlated with age (p < .001) and sex (p = .004). In the comparison of the healthy, DM and HS groups, patients with DM had a significantly increased SULmean, whereas patients with HS had a significantly decreased DV. CONCLUSIONS: Our results showed that liver glucose metabolism was influenced by various patient characteristic factors. Multiparametric FDG-PET imaging can be used to analyse the kinetics of liver glucose metabolism in routine clinical practice.

Eribulin improves tumor oxygenation demonstrated by 18F-DiFA hypoxia imaging, leading to radio-sensitization in human cancer xenograft models.

PURPOSE: Eribulin, an inhibitor of microtubule dynamics, is known to show antitumor effects through its remodeling activity in the tumor vasculature. However, the extent to which the improvement of tumor hypoxia by eribulin affects radio-sensitivity remains unclear. We utilized 1-(2,2-dihydroxymethyl-3-18F-fluoropropyl)-2-nitroimidazole (18F-DiFA), a new PET probe for hypoxia, to investigate the effects of eribulin on tumor hypoxia and evaluate the radio-sensitivity during eribulin treatment. METHODS: Mice bearing human breast cancer MDA-MB-231 cells or human lung cancer NCI-H1975 cells were administered a single dose of eribulin. After administration, mice were injected with 18F-DiFA and pimonidazole, and tumor hypoxia regions were analyzed. For the group that received combined treatment with radiation, 18F-DiFA PET/CT imaging was performed before tumors were locally X-irradiated. Tumor size was measured every other day after irradiation. RESULTS: Eribulin significantly reduced 18F-DiFA accumulation levels in a dose-dependent manner. Furthermore, the reduction in 18F-DiFA accumulation levels by eribulin was most significant 7 days after treatment. These results were also supported by reduction of the pimonidazole-positive hypoxic region. The combined treatment showed significant retardation of tumor growth in comparison with the control, radiation-alone, and drug-alone groups. Importantly, tumor growth after irradiation was inversely correlated with 18F-DiFA accumulation. CONCLUSION: These results demonstrated that 18F-DiFA PET/CT clearly detected eribulin-induced tumor oxygenation and that eribulin efficiently enhanced the antitumor activity of radiation by improving tumor oxygenation.

Determination of brain tumor recurrence using 11 C-methionine positron emission tomography after radiotherapy.

We conducted a prospective multicenter trial to compare the usefulness of 11 C-methionine (MET) and 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for identifying tumor recurrence. Patients with clinically suspected tumor recurrence after radiotherapy underwent both 11 C-MET and 18 F-FDG PET. When a lesion showed a visually detected uptake of either tracer, it was surgically resected for histopathological analysis. Patients with a lesion negative to both tracers were revaluated by magnetic resonance imaging (MRI) at 3 months after the PET studies. The primary outcome measure was the sensitivity of each tracer in cases with histopathologically confirmed recurrence, as determined by the McNemar test. Sixty-one cases were enrolled, and 56 cases could be evaluated. The 38 cases where the lesions showed uptake of either 11 C-MET or 18 F-FDG underwent surgery; 32 of these cases were confirmed to be subject to recurrence. Eighteen cases where the lesions showed uptake of neither tracer received follow-up MRI; the lesion size increased in one of these cases. Among the cases with histologically confirmed recurrence, the sensitivities of 11 C-MET PET and 18 F-FDG PET were 0.97 (32/33, 95% confidence interval [CI]: 0.85-0.99) and 0.48 (16/33, 95% CI: 0.33-0.65), respectively, and the difference was statistically significant (P < .0001). The diagnostic accuracy of 11 C-MET PET was significantly better than that of 18 F-FDG PET (87.5% vs. 69.6%, P = .033). No examination-related adverse events were observed. The results of the study demonstrated that 11 C-MET PET was superior to 18 F-FDG PET for discriminating between tumor recurrence and radiation-induced necrosis.

18F-FMISO PET/CT detects hypoxic lesions of cardiac and extra-cardiac involvement in patients with sarcoidosis.

BACKGROUND: 18F-fluoromisonidazole (FMISO) is a hypoxia positron emission tomography (PET) tracer. Here, we evaluated cardiac and extra-cardiac sarcoidosis using both FMISO and 18F-fluorodeoxyglucose (FDG) PET/CT in a prospective cohort of patients with sarcoidosis. METHODS: Ten consecutive sarcoidosis patients with suspected cardiac involvement were prospectively enrolled. Each patient fasted overnight (for ≥ 18 hours) preceded by a low-carbohydrate diet before FDG PET/CT but not given special dietary instructions before the FMISO PET/CT scan. We visually and semiquantitatively assessed the uptakes of FMISO and FDG using the maximal standardized uptake value (SUVmax). The metabolic volume (MV) of FDG was calculated as the volume within the boundary determined by the threshold (mean SUV of blood pool × 1.5). RESULTS: Nine patients showed focal FDG uptake in the myocardium and were diagnosed with cardiac sarcoidosis. Among the patients with extra-cardiac lesions, FDG uptake was seen in 8 lymph nodes and 3 lung lesions. FMISO uptake was seen in the 7 cardiac (77.8%) and 6 extra-cardiac (54.5%) lesions. None of the patients showed physiological FMISO uptake in the myocardium. The SUVmax values of the lesions with FMISO uptake were higher than those of the lesions without FMISO uptake in both the cardiac (SUVmax: 9.9, IQR: 8.4-10.0 vs 7.3, IQR: 6.3-8.2) and non-cardiac lesions (SUVmax: 17.6, IQR: 14.5-19.3 vs 6.1, IQR: 5.9-6.2; P = 0.006). The MV values of the lesions with FMISO uptake were significantly higher than those of the lesions without FMISO uptake (111.3, IQR: 78.3-135.7 vs 6.4, IQR: 1.9-23.3; P = 0.0009). CONCLUSIONS: FMISO showed no physiological myocardial uptake and did not require special preparation. FMISO PET has the potential to detect hypoxic lesions in patients with sarcoidosis.

Correlation of active contact location with weight gain after subthalamic nucleus deep brain stimulation: a case series.

BACKGROUND: Weight gain (WG) is a frequently reported side effect of subthalamic deep brain stimulation; however, the underlying mechanisms remain unclear. The active contact locations influence the clinical outcomes of subthalamic deep brain stimulation, but it is unclear whether WG is directly associated with the active contact locations. We aimed to determine whether WG is associated with the subthalamic deep brain stimulation active contact locations. METHODS: We enrolled 14 patients with Parkinson's disease who underwent bilateral subthalamic deep brain stimulation between 2013 and 2019. Bodyweight and body mass index were measured before and one year following the surgery. The Lead-DBS Matlab toolbox was used to determine the active contact locations based on magnetic resonance imaging and computed tomography. We also created sweet spot maps for WG using voxel-wise statistics, based on volume of tissue activation and the WG of each patient. Fluorodeoxyglucose-positron emission tomography data were also acquired before and one year following surgery, and statistical parametric mapping was used to evaluate changes in brain metabolism. We examined which brain regions' metabolism fluctuation significantly correlated with increased body mass index scores and positron emission tomography data. RESULTS: One year after surgery, the body mass index increase was 2.03 kg/m2. The sweet spots for WG were bilateral, mainly located dorsally outside of the subthalamic nucleus (STN). Furthermore, WG was correlated with increased metabolism in the left limbic and associative regions, including the middle temporal gyrus, inferior frontal gyrus, and orbital gyrus. CONCLUSIONS: Although the mechanisms underlying WG following subthalamic deep brain stimulation are possibly multifactorial, our findings suggest that dorsal stimulation outside of STN may lead to WG. The metabolic changes in limbic and associative cortical regions after STN-DBS may also be one of the mechanisms underlying WG. Further studies are warranted to confirm whether dorsal stimulation outside of STN changes the activities of these cortical regions.

Clinical Perspectives of Theranostics.

Theranostics is a precision medicine which integrates diagnostic nuclear medicine and radionuclide therapy for various cancers throughout body using suitable tracers and treatment that target specific biological pathways or receptors. This review covers traditional theranostics for thyroid cancer and pheochromocytoma with radioiodine compounds. In addition, recent theranostics of radioimmunotherapy for non-Hodgkin lymphoma, and treatment of bone metastasis using bone seeking radiopharmaceuticals are described. Furthermore, new radiopharmaceuticals for prostatic cancer and pancreatic cancer have been added. Of particular, F-18 Fluoro-2-Deoxyglucose (FDG) Positron Emission Tomography (PET) is often used for treatment monitoring and estimating patient outcome. A recent clinical study highlighted the ability of alpha-radiotherapy with high linear energy transfer (LET) to overcome treatment resistance to beta--particle therapy. Theranostics will become an ever-increasing part of clinical nuclear medicine.

Influence of the scan time point when assessing hypoxia in 18F-fluoromisonidazole PET: 2 vs. 4 h.

PURPOSE: 18F-fluoromisonidazole (18F-FMISO) is the most widely used positron emission tomography (PET) tracer for imaging tumor hypoxia. Previous reports suggested that the time from injection to the scan may affect the assessment of 18F-FMISO uptake. Herein, we directly compared the images at 2 h and 4 h after a single injection of 18F-FMISO. METHODS: Twenty-three patients with or suspected of having a brain tumor were scanned twice at 2 and 4 h following an intravenous injection of 18F-FMISO. We estimated the mean standardized uptake value (SUV) of the gray matter and white matter and the gray-to-white matter ratio in the background brain tissue from the two scans. We also performed a semi-quantitative analysis using the SUVmax and maximum tumor-to-normal ratio (TNR) for the tumor. RESULTS: At 2 h, the SUVmean of gray matter was significantly higher than that of white matter (median 1.23, interquartile range (IQR) 1.10-1.32 vs. 1.04, IQR 0.95-1.16, p < 0.0001), whereas at 4 h, it significantly decreased to approach that of the white matter (1.10, IQR 1.00-1.23 vs. 1.02, IQR 0.93-1.13, p = NS). The gray-to-white matter ratio thus significantly declined from 1.17 (IQR 1.14-1.19) to 1.09 (IQR 1.07-1.10) (p < 0.0001). All 7 patients with glioblastoma showed significant increases in the SUVmax (2.20, IQR 1.67-3.32 at 2 h vs. 2.65, IQR 1.74-4.41 at 4 h, p = 0.016) and the TNR (1.75, IQR 1.40-2.38 at 2 h vs. 2.34, IQR 1.67-3.60 at 4 h, p = 0.016). CONCLUSION: In the assessment of hypoxic tumors, 18F-FMISO PET for hypoxia imaging should be obtained at 4 h rather than 2 h after the injection.

A convolutional neural network-based system to classify patients using FDG PET/CT examinations.

BACKGROUND: As the number of PET/CT scanners increases and FDG PET/CT becomes a common imaging modality for oncology, the demands for automated detection systems on artificial intelligence (AI) to prevent human oversight and misdiagnosis are rapidly growing. We aimed to develop a convolutional neural network (CNN)-based system that can classify whole-body FDG PET as 1) benign, 2) malignant or 3) equivocal. METHODS: This retrospective study investigated 3485 sequential patients with malignant or suspected malignant disease, who underwent whole-body FDG PET/CT at our institute. All the cases were classified into the 3 categories by a nuclear medicine physician. A residual network (ResNet)-based CNN architecture was built for classifying patients into the 3 categories. In addition, we performed a region-based analysis of CNN (head-and-neck, chest, abdomen, and pelvic region). RESULTS: There were 1280 (37%), 1450 (42%), and 755 (22%) patients classified as benign, malignant and equivocal, respectively. In the patient-based analysis, CNN predicted benign, malignant and equivocal images with 99.4, 99.4, and 87.5% accuracy, respectively. In region-based analysis, the prediction was correct with the probability of 97.3% (head-and-neck), 96.6% (chest), 92.8% (abdomen) and 99.6% (pelvic region), respectively. CONCLUSION: The CNN-based system reliably classified FDG PET images into 3 categories, indicating that it could be helpful for physicians as a double-checking system to prevent oversight and misdiagnosis.

Competition between Conversion Reaction with Cerium Dioxide and Lithium Plating in Superconcentrated Electrolyte.

Li-ion insertion into cerium dioxide (CeO2) and its subsequent conversion reaction were studied using a CeO2/copper composite electrode in a superconcentrated electrolyte of lithium bis(fluorosulfonyl)amide (LiFSA) and methylphenylamino-di(trifluoroethyl) phosphate (PNMePh) under conditions promoting Li plating/stripping. Since the conversion reaction potential with CeO2 generally lies above the Li plating/stripping level, the conversion ideally occurs first in the cathodic scan. However, the conversion reaction was delayed until after the Li plating in the superconcentrated electrolyte contrary to expectations, whereas this phenomenon was unobserved in a dilute LiFSA/PNMePh electrolyte. Energy-dispersive X-ray spectroscopy and electrochemical impedance analysis indicated that the reversed order of the electrochemical behaviors was caused by the solid electrolyte interphase (SEI) on the CeO2, which had a different material composition and a higher interfacial resistance than the SEI on electrodeposited metallic lithium.

Volume-based glucose metabolic analysis of FDG PET/CT: The optimum threshold and conditions to suppress physiological myocardial uptake.

OBJECTIVE: FDG PET/CT plays a significant role in the diagnosis of inflammatory heart diseases and cardiac tumors. We attempted to determine the optimal FDG uptake threshold for volume-based analyses and to evaluate the relationship between the myocardial physiological uptake volume in FDG PET and several clinical factors. METHODS: A total of 190 patients were retrospectively analyzed. The cardiac metabolic volume (CMV) was defined as a volume within the boundary determined by a threshold (SUVmean of blood pool × 1.5). RESULTS: The SUVmean of the blood pool measured in the descending aorta (DA) (r = 0.86, intraclass correlation coefficient [ICC] = 0.93, P < 0.0001) and that in the left ventricle (LV) cavity (r = 0.87, ICC = 0.90, P < 0.0001) showed high inter-operator reproducibility. However, the SUVmean in the LV cavity showed a significant correlation with the CMV (P = 0.0002, r = 0.26). The CMV in the patients who fasted < 18 hours were significantly higher (49.7  ±  73.2 vs. 18.0  ±  53.8 mL, P = 0.0013) compared to the patients with > 18-hour fasting. The multivariate analysis demonstrated that only the fasting period > 18 hours was independently associated with CMV = 0. CONCLUSION: Our findings revealed that the DA is suitable to decide the threshold for the volume-based analysis. The fasting time was significantly associated with the cardiac FDG uptake.

[A Case of WDHA Water Diarrhea Hypokalemia Achlorhydria Syndrome that Developed after Multimodal Therapy for Retroperitoneal Paraganglioma].

A 45-year-old woman visited a local clinic with left-flank abdominal pain. Abdominal computed tomography (CT) revealed a tumor 20 cm in diameter in the left adrenal gland. She was referred to our hospital for further treatment. No endocrinological abnormality was detected on either serum or urine examination. CT and haematology findings led to a preoperative diagnosis of primary adrenal carcinoma, and we performed a left adrenalectomy. Histopathological examination revealed a paraganglioma with intact adrenal gland. Therefore we diagnosed this case as primary retroperitoneal paraganglioma. Six months after the surgery, she developed peritoneal dissemination including bilateral ovarian metastases. After cytoreductive metastasectomy, she received 131I-meta-iodobenzylguanidine (MIBG) radiotherapy. During the following five-year follow-up, MIBG radiotherapy in conjunction with cytoreductive metastasectomy (3 surgeries and 6 sessions of 131I-MIBG radiotherapy) was performed, aiming at disease control. Five years after the initial surgery, liver, lung, and intra-peritoneal dissemination progressed. Thereafter, she developed severe diarrhea, hypokalemia, and metabolic acidosis with an elevated level of vasoactive intestional peptide, which was consistent with water diarrhea, hypokalemia, achlorhydria (WDHA) syndrome. Despite intensive treatments such as with a somatostatin analogue, she died two months after the onset of this syndrome.

Relationship between intelligence quotient (IQ) and cerebral metabolic rate of oxygen in patients with neurobehavioural disability after traumatic brain injury.

OBJECTIVE: Cerebral metabolism may play a significant role in neurobehavioural disability following traumatic brain injury (TBI). In this study, we examined the relationship between intelligence quotient (IQ) and the cerebral metabolic rate of oxygen (CMRO2) in the lateral prefrontal cortex, which was measured by 15O-labelled gas positron emission tomography (PET), in patients with TBI. MATERIALS AND METHODS: The subjects were 12 patients (eight males and four females) who suffered from neurobehavioural disability following TBI. Their mean age was 33.3 years. The cause of injury was traffic accidents in all patients and the mean period after injury was 44.8 months. These patients underwent 15O-labelled gas PET and tests using either the Wechsler Adult Intelligence Scale-Revised (WAIS-R) or the Wechsler Intelligence Scale for Children-Revised (WISC-R). Pearson's correlation between CMRO2 and total IQ (TIQ) was calculated. RESULTS: A statistically significant correlation was observed between TIQ and CMRO2 in the right Brodmann areas (BAs) 44 and 45. The lower the WAIS score, the higher the CMRO2 in both areas. CONCLUSION: Neurological function negatively correlated with the metabolism of oxygen. It was possible that changes in brain networks increased the neuronal activity in the undamaged areas and that the increased activity compensated for the function decline.

Hypoxic glucose metabolism in glioblastoma as a potential prognostic factor.

PURPOSE: Metabolic activity and hypoxia are both important factors characterizing tumor aggressiveness. Here, we used F-18 fluoromisonidazole (FMISO) and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) to define metabolically active hypoxic volume, and investigate its clinical significance in relation to progression free survival (PFS) and overall survival (OS) in glioblastoma patients. EXPERIMENTAL DESIGN: Glioblastoma patients (n = 32) underwent FMISO PET, FDG PET, and magnetic resonance imaging (MRI) before surgical intervention. FDG and FMISO PET images were coregistered with gadolinium-enhanced T1-weighted MR images. Volume of interest (VOI) of gross tumor volume (GTV) was manually created to enclose the entire gadolinium-positive areas. The FMISO tumor-to-normal region ratio (TNR) and FDG TNR were calculated in a voxel-by-voxel manner. For calculating TNR, standardized uptake value (SUV) was divided by averaged SUV of normal references. Contralateral frontal and parietal cortices were used as the reference region for FDG, whereas the cerebellar cortex was used as the reference region for FMISO. FDG-positive was defined as the FDG TNR ≥1.0, and FMISO-positive was defined as FMISO TNR ≥1.3. Hypoxia volume (HV) was defined as the volume of FMISO-positive and metabolic tumor volume in hypoxia (hMTV) was the volume of FMISO/FDG double-positive. The total lesion glycolysis in hypoxia (hTLG) was hMTV × FDG SUVmean. The extent of resection (EOR) involving cytoreduction surgery was volumetric change based on planimetry methods using MRI. These factors were tested for correlation with patient prognosis. RESULTS: All tumor lesions were FMISO-positive and FDG-positive. Univariate analysis indicated that hMTV, hTLG, and EOR were significantly correlated with PFS (p = 0.007, p = 0.04, and p = 0.01, respectively) and that hMTV, hTLG, and EOR were also significantly correlated with OS (p = 0.0028, p = 0.037, and p = 0.014, respectively). In contrast, none of FDG TNR, FMISO TNR, GTV, HV, patients' age, or Karnofsky performance scale (KPS) was significantly correlated with PSF or OS. The hMTV and hTLG were found to be independent factors affecting PFS and OS on multivariate analysis. CONCLUSIONS: We introduced hMTV and hTLG using FDG and FMISO PET to define metabolically active hypoxic volume. Univariate and multivariate analyses demonstrated that both hMTV and hTLG are significant predictors for PFS and OS in glioblastoma patients.

18F-fluoromisonidazole (FMISO) PET may have the potential to detect cardiac sarcoidosis.

18F-fluoromisonidazole (FMISO) is a positron emission tomography (PET) tracer that accumulates in hypoxic tissues. We here present a case of suspected cardiac sarcoidosis which was detected with increased FMISO uptake.

The reoxygenation of hypoxia and the reduction of glucose metabolism in head and neck cancer by fractionated radiotherapy with intensity-modulated radiation therapy.

PURPOSE: The purpose of this study was to prospectively investigate reoxygenation in the early phase of fractionated radiotherapy and serial changes of tumoricidal effects associated with intensity-modulated radiation therapy (IMRT) in patients with head and neck cancer (HNC) using F-18 fluoromisonidazole (FMISO) PET and F-18 fluorodeoxyglucose (FDG) PET. METHODS: Patients with untreated HNC underwent FMISO-PET and FDG-PET studies prospectively. A PET evaluation was conducted before each IMRT (Pre-IMRT), during IMRT (at 30 Gy/15 fr) (Inter-IMRT), and after completion of IMRT (70 Gy/35 fr) (Post-IMRT). FMISO-PET images were scanned by a PET/CT scanner at 4 h after the FMISO injection. We quantitatively analyzed the FMISO-PET images of the primary lesion using the maximum standardized uptake (SUVmax) and tumor-to-muscle ratio (TMR). The hypoxic volume (HV) was calculated as an index of tumor hypoxia, and was defined as the volume when the TMR was ≥ 1.25. Each FDG-PET scan was started 1 h after injection. The SUVmax and metabolic tumor volume (MTV) values obtained by FDG-PET were analyzed. RESULTS: Twenty patients finished the complete PET study protocol. At Pre-IMRT, 19 patients had tumor hypoxia in the primary tumor. In ten patients, the tumor hypoxia disappeared at Inter-IMRT. Another seven patients showed the disappearance of tumor hypoxia at Post-IMRT. Two patients showed tumor hypoxia at Post-IMRT. The FMISO-PET results showed that the reduction rates of both SUVmax and TMR from Pre-IMRT to Inter-IMRT were significantly higher than the corresponding reductions from Inter-IMRT to Post-IMRT (SUVmax: 27 % vs. 10 %, p = 0.025; TMR: 26 % vs. 12 %, p = 0.048). The reduction rate of SUVmax in FDG-PET from Pre-IMRT to Inter-IMRT was similar to that from Inter-IMRT to Post-IMRT (47 % vs. 48 %, p = 0.778). The reduction rate of the HV in FMISO-PET from Pre-IMRT to Inter-IMRT tended to be larger than that from Inter-IMRT to Post-IMRT (63 % vs. 40 %, p = 0.490). Conversely, the reduction rate of the MTV in FDG-PET from Pre-IMRT to Inter-IMRT was lower than that from Inter-IMRT to Post-IMRT (47 % vs. 74 %, p = 0.003). CONCLUSIONS: Both the intensity and the volume of tumor hypoxia rapidly decreased in the early phase of radiotherapy, indicating reoxygenation of the tumor hypoxia. In contrast, the FDG uptake declined gradually with the course of radiotherapy, indicating that the tumoricidal effect continues over the entire course of radiation treatment.

(18)F-fluoromisonidazole positron emission tomography can predict pathological necrosis of brain tumors.

PURPOSE: Tumor necrosis is one of the indicators of tumor aggressiveness. (18)F-fluoromisonidazole (FMISO) is the most widely used positron emission tomography (PET) tracer to evaluate severe hypoxia in vivo. Because severe hypoxia causes necrosis, we hypothesized that intratumoral necrosis can be detected by FMISO PET in brain tumors regardless of their histopathology. We applied FMISO PET to various types of brain tumors before tumor resection and evaluated the correlation between histopathological necrosis and FMISO uptake. METHODS: This study included 59 brain tumor patients who underwent FMISO PET/computed tomography before any treatments. According to the pathological diagnosis, the brain tumors were divided into three groups: astrocytomas (group 1), neuroepithelial tumors except for astrocytomas (group 2), and others (group 3). Two experienced neuropathologists evaluated the presence of necrosis in consensus. FMISO uptake in the tumor was evaluated visually and semi-quantitatively using the tumor-to-normal cerebellum ratio (TNR). RESULTS: In visual analyses, 26/27 cases in the FMISO-positive group presented with necrosis, whereas 28/32 cases in the FMISO-negative group did not show necrosis. Mean TNRs with and without necrosis were 3.49 ± 0.97 and 1.43 ± 0.42 (p < 0.00001) in group 1, 2.91 ± 0.83 and 1.44 ± 0.20 (p < 0.005) in group 2, and 2.63 ± 1.16 and 1.35 ± 0.23 (p < 0.05) in group 3, respectively. Using a cut-off value of TNR = 1.67, which was calculated by normal reference regions of interest, we could predict necrosis with sensitivity, specificity, and accuracy of 96.7, 93.1, and 94.9 %, respectively. CONCLUSIONS: FMISO uptake within the lesion indicated the presence of histological micro-necrosis. When we used a TNR of 1.67 as the cut-off value, intratumoral micro-necrosis was sufficiently predictable. Because the presence of necrosis implies a poor prognosis, our results suggest that FMISO PET could provide important information for treatment decisions or surgical strategies of any type of brain tumor.

Use of FDG-PET to detect a chronic odontogenic infection as a possible source of the brain abscess.

This study describes the use of (18)F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) to detect a chronic odontogenic infection as the possible origin of a brain abscess (BA). A 74-year-old man with esophageal carcinoma was referred to our department to determine the origin of a BA in his oral cavity. He had no acute odontogenic infections. The BA was drained, and bacteria of the Staphylococcus milleri group were detected. Whole body FDG-PET revealed that the only sites of definite uptake of FDG were the esophageal carcinoma and the left upper maxillary region (SUVmax: 4.5). These findings suggested that the BA may have originated from a chronic periodontal infection. Six teeth with progressive chronic periodontal disease were extracted to remove the possible source of BA. These findings excluded the possibility of direct spread of bacteria from the odontogenic infectious lesion to the intracranial cavity. After extraction, there was no relapse of BA.

Prognostic value of volume-based measurements on (11)C-methionine PET in glioma patients.

PURPOSE: (11)C-methionine (MET) PET is an established diagnostic tool for glioma. Studies have suggested that MET uptake intensity in the tumor is a useful index for predicting patient outcome. Because MET uptake is known to reflect tumor expansion more accurately than MRI, we aimed to elucidate the association between volume-based tumor measurements and patient prognosis. METHODS: The study population comprised 52 patients with newly diagnosed glioma who underwent PET scanning 20 min after injection of 370 MBq MET. The tumor was contoured using a threshold of 1.3 times the activity of the contralateral normal cortex. Metabolic tumor volume (MTV) was defined as the total volume within the boundary. Total lesion methionine uptake (TLMU) was defined as MTV times the mean standardized uptake value (SUVmean) within the boundary. The tumor-to-normal ratio (TNR), calculated as the maximum standardized uptake value (SUVmax) divided by the contralateral reference value, was also recorded. All patients underwent surgery (biopsy or tumor resection) targeting the tissue with high MET uptake. The Kaplan-Meier method was used to estimate the predictive value of each measurement. RESULTS: Grade II tumor was diagnosed in 12 patients (3 diffuse astrocytoma, 2 oligodendroglioma, and 7 oligoastrocytoma), grade III in 18 patients (8 anaplastic astrocytoma, 6 anaplastic oligodendroglioma, and 4 anaplastic oligoastrocytoma), and grade IV in 22 patients (all glioblastoma). TNR, MTV and TLMU were 3.1 ± 1.2, 51.6 ± 49.9 ml and 147.7 ± 153.3 ml, respectively. None of the three measurements was able to categorize the glioma patients in terms of survival when all patients were analyzed. However, when only patients with astrocytic tumor (N = 33) were analyzed (i.e., when those with oligodendroglial components were excluded), MTV and TLMU successfully predicted patient outcome with higher values associated with a poorer prognosis (P < 0.05 and P < 0.01, respectively), while the predictive ability of TNR did not reach statistical significance (P = NS). CONCLUSION: MTV and TLMU may be useful for predicting outcome in patients with astrocytic tumor.

Oligodendroglial component complicates the prediction of tumour grading with metabolic imaging.

PURPOSE: Previous radiological investigations have generally shown the superiority of metabolic imaging in distinguishing high-grade from low-grade glioma, but the presence of an oligodendroglial component may affect the diagnostic accuracy. We investigated the diagnostic accuracy of PET imaging using (11)C-methionine (MET) and (18)F-fluorodeoxyglucose (FDG) in distinguishing high-grade from low-grade glioma, in correlation with the oligodendroglial component. METHODS: The study population comprised adult patients who underwent preoperative PET imaging using both MET and FDG within 1 week and successful excision of the tumour tissue, which confirmed WHO grade II-IV glioma. We examined the tumour metabolic activity in terms of lesion-to-normal uptake ratios (L/N ratio) in both MET PET and FDG PET images. We assessed the correlation between the imaging results and the histological findings to determine the diagnostic accuracy of receiver operating characteristics (ROC) analysis in detecting high-grade tumours. RESULTS: We studied 46 patients with glioma (13 low-grade and 33 high-grade), including 26 with an oligodendroglial components. The L/N ratios of the PET images showed significantly higher metabolic activities in high-grade gliomas than in low-grade gliomas for both MET (4.29 ± 1.22 and 2.36 ± 0.72, respectively; p < 0.0001) and FDG (1.72 ± 0.91 and 0.77 ± 0.26, respectively; p = 0.0007) images, although significant overlaps in L/N ratio were observed between high-grade and low-grade gliomas. Excluding the 26 patents with an oligodendroglial component improved the separation for both MET (4.62 ± 1.14 vs. 2.16 ± 0.63; p < 0.001) and FDG (1.76 ± 0.87 vs. 0.71 ± 0.14; p < 0.05) images. The ROC analyses demonstrated the clinical utility of the metabolic radiotracers in distinguishing high-grade from low-grade gliomas, showing similar AUC values for MET (0.91) and FDG (0.92). Excluding the 26 patents with an oligodendroglial component also further improved the diagnostic accuracy for both MET (AUC 0.98), and FDG (AUC 1.00) images. The metabolic radiotracers were significantly correlated with the MIB-1 labelling index (R = 0.52, p < 0.05 for MET; R = 0.52, p < 0.05, for FDG) only in gliomas without an oligodendroglial component. CONCLUSION: For better characterization of gliomas and for risk assessment, the results of metabolic PET imaging should be revised after obtaining the pathological report, because oligodendroglial differentiation may positively influence the substrate metabolism and thus complicated the preoperative evaluation.