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Abstract Background The goal of the study was to evaluate the diagnostic ability of 18F-FBPA PET/CT for malignant tumors. Findings from 18F-FBPA and 18F-FDG PET/CT were compared with pathological diagnoses in patients with malignant tumors or benign lesions. Methods A total of 82 patients (45 males, 37 females; median age, 63 years; age range, 20–89 years) with various types of malignant tumors or benign lesions, such as inflammation and granulomas, were examined by 18F-FDG and 18F-FBPA PET/CT. Tumor uptake of FDG or FBPA was quantified using the maximum standardized uptake value (SUVmax). The final diagnosis was confirmed by cytopathology or histopathological findings of the specimen after biopsy or surgery. A ROC curve was constructed from the SUVmax values of each PET image, and the area under the curve (AUC) and cutoff values were calculated. Results The SUVmax for 18F-FDG PET/CT did not differ significantly for malignant tumors and benign lesions (10.9 ± 6.3 vs. 9.1 ± 2.7 P = 0.62), whereas SUVmax for 18F-FBPA PET/CT was significantly higher for malignant tumors (5.1 ± 3.0 vs. 2.9 ± 0.6, P

Abstract Boron neutron capture therapy (BNCT) for the treatment of unresectable, locally advanced, and recurrent carcinoma of the head and neck cancer has been approved by the Japanese government for reimbursement under the national health insurance as of June 2020. A new treatment planning system for clinical BNCT has been developed by Sumitomo Heavy Industries, Ltd. (Sumitomo), NeuCure® Dose Engine. To safely implement this system for clinical use, the simulated neutron flux and gamma ray dose rate inside a water phantom was compared against experimental measurements. Furthermore, to validate and verify the new planning system, the dose distribution inside an anthropomorphic head phantom was compared against a BNCT treatment planning system SERA and an in-house developed Monte Carlo dose calculation program. The simulated results closely matched the experimental results, within 5% for the thermal neutron flux and 10% for the gamma ray dose rate. The dose distribution inside the head phantom closely matched with SERA and the in-house developed dose calculation program, within 3% for the tumour and a difference of 0.3 Gyw for the brain.

Summary: Nociceptors can fine-tune local or systemic immunity, but the mechanisms of nociceptive modulation in endotoxic death remain largely unknown. Here, we identified C-type lectin Reg3γ as a nociceptor-enriched hormone that protects the host from endotoxic death. During endotoxemia, nociceptor-derived Reg3γ penetrates the brain and suppresses the expression of microglial indoleamine dioxygenase 1, a critical enzyme of the kynurenine pathway, via the Extl3-Bcl10 axis. Endotoxin-administered nociceptor-null mice and nociceptor-specific Reg3γ-deficient mice exhibit a high mortality rate accompanied by decreased brain HK1 phosphorylation and ATP production despite normal peripheral inflammation. Such metabolic arrest is only observed in the brain, and aberrant production of brain quinolinic acid, a neurotoxic metabolite of the kynurenine pathway, causes HK1 suppression. Strikingly, the central administration of Reg3γ protects mice from endotoxic death by enhancing brain ATP production. By identifying nociceptor-derived Reg3γ as a microglia-targeted hormone, this study provides insights into the understanding of tolerance to endotoxic death.

Summary: Intravenously injected ONO-1301–containing nanoparticles (ONO-1301NPs), unlike an ONO-1301 solution, selectively accumulated in the ischemia/reperfusion (I/R)-injured myocardium of rats and contributed to the prolonged retention of ONO-1301 in the targeted myocardial tissue. In the ischemic area, proangiogenic cytokines were up-regulated and inflammatory cytokines were down-regulated upon ONO-1301NP administration. Consequently, ONO-1301NP–injected rats exhibited a smaller infarct size, better-preserved capillary networks, and a better-preserved myocardial blood flow at 24 h after I/R injury, compared with those in vehicle-injected or ONO-1301 solution–injected rats. ONO-1301NPs attenuate the myocardial I/R injury via proangiogenic and anti-inflammatory effects of the drug. Key Words: ischemia/reperfusion injury, nanoparticles, ONO-1301, prostacyclin

Objective(s): Renography is used for the diagnostic evaluation of pediatric patients with a suspected obstruction of urinary tract or impaired renal function. The recommended dose for children have been released by the European Association of Nuclear Medicine, Society of Nuclear Medicine and Molecular Imaging, and Japanese Society of Nuclear Medicine. Since acquisition counts in dynamic scintigraphy are affected by the administered doses and sensitivity of the scintillation camera, the scan procedure should be determined independently. In this study, we constructed simplified dynamic phantom imitating pediatric renography and tested its performance.Methods: Simplified dynamic phantom consisted of three components (i.e.,infusion, imitated kidney, and drainage sections). The infusion rates (mL/min) were determined by comparing the time activity curves obtained from patientswith normal renal function. The time-points of the maximum counts (Tmax), as well as the two-thirds and one-half of the maximum counts (T2/3 and T1/2) were measured in different doses using the phantom with the best-match infusion rateand duration, and low-energy general-purpose (LEGP) or low-energy highresolution (LEHR) collimators and applying different attenuations.Results: The best-match infusion rates of the phantom to imitate the time activity curve of the normal renal function were 42.0, 1.0, 0.6, and 0.3 mL/min in the arterial, secretory, early-excretory, and late-excretory phases, respectively. When 30 MBq, LEHR collimator and non-water-equivalent phantom were applied, Tmax, T2/3, and T1/2 were 242±15.3, 220±10.0 and 317±25.2 seconds, respectively. Using LEGP collimator and (3 MBq of activity) 5-cm water-equivalent phantom, Tmax, T2/3, and T1/2 values were estimated as 242±5.8, 213±11.5, and 310±17.3 sec, respectively.Conclusion: Our simplified dynamic phantom for pediatric renography could imitate the time activity curves obtained from patients with normal renal function. Tmax, T2/3, and T1/2 could be measured under various settings of dose,collimator, and tissue attenuation.

Assessment of tumor response during treatment is one of the most important purposes of imaging. Before the appearance of immunotherapy, response evaluation criteria in solid tumors (RECIST) and positron emission tomography response criteria in solid tumors (PERCIST) were, respectively, the established morphologic and metabolic response criteria, and cessation of treatment was recommended when progressive disease was detected according to these criteria. However, various types of immunotherapy have been developed over the past 20 years, which show novel false positive findings on images, as well as distinct response patterns from conventional therapies. Antitumor immune response itself causes 18F-fluorodeoxyglucose (FDG) uptake in tumor sites, known as “flare phenomenon”, so that positron emission tomography using FDG can no longer accurately identify remaining tumors. Furthermore, tumors often initially increase, followed by stability or decrease resulting from immunotherapy, which is called “pseudoprogression”, so that progressive disease cannot be confirmed by computed tomography or magnetic resonance imaging at a single time point. As a result, neither RECIST nor PERCIST can accurately predict the response to immunotherapy, and therefore several new response criteria fixed for immunotherapy have been proposed. However, these criteria are still controversial, and also require months for response confirmation. The establishment of optimal response criteria and the development of new imaging technologies other than FDG are therefore urgently needed. In this review, we summarize the false positive images and the revision of response criteria for each immunotherapy, in order to avoid discontinuation of a truly effective immunotherapy.

Abstract Background Positron emission tomography (PET) studies using 15O-labeled CO2, O2, and CO have been used in humans to evaluate cerebral blood flow (CBF), the cerebral oxygen extraction fraction (OEF), and the cerebral metabolic rate of oxygen (CMRO2) and cerebral blood volume (CBV), respectively. In preclinical studies, however, PET studies using 15O-labeled gases are not widely performed because of the technical difficulties associated with handling labeled gases with a short half-life. The aims of the present study were to evaluate the scatter fraction using 3D-mode micro-PET for 15O-labeled gas studies and the influence of reconstruction algorithms on quantitative values. Nine male SD rats were studied using the steady state inhalation method for 15O-labeled gases with arterial blood sampling. The resulting PET images were reconstructed using filtered back projection (FBP), ordered-subset expectation maximization (OSEM) 2D, or OSEM 3D followed by maximum a posteriori (OSEM3D-MAP). The quantitative values for each brain region and each reconstruction method were calculated by applying different reconstruction methods. Results The quantitative values for the whole brain as calculated using FBP were 46.6 ± 12.5 mL/100 mL/min (CBF), 63.7 ± 7.2% (OEF), 5.72 ± 0.34 mL/100 mL/min (CMRO2), and 5.66 ± 0.34 mL/100 mL (CBV), respectively. The CBF and CMRO2 values were significantly higher when the OSEM2D and OSEM3D-MAP reconstruction methods were used, compared with FBP, whereas the OEF values were significantly lower when reconstructed using OSEM3D-MAP. Conclusions We evaluated the difference in quantitative values among the reconstruction algorithms using 3D-mode micro-PET. The iterative reconstruction method resulted in significantly higher quantitative values for CBF and CMRO2, compared with the values calculated using the FBP reconstruction method.

Objective(s): This study aimed to evaluate the role of pretreatment SUVmax and volumetric FDG positron emission tomography (PET) parameters in the differentiation between benign and malignant mediastinal tumors. In addition, we investigated whether pretreatment SUVmax and volumetric FDG-PET parameters could distinguish thymomas from thymic carcinomas, and low-risk from high-risk thymomas.Methods: This study was conducted on 52 patients with mediastinal tumors undergoing FDG-PET/CT. Histological examination indicated that 29 mediastinal tumors were benign, and 23 cases were malignant. To obtain quantitative PET/CT parameters, we determined the maximum standardized uptake value (SUVmax), volumetric parameters, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for primary tumors using SUVmax cut-off value of 2.5. SUVmax, MTV and TLG of benign and malignant tumors were comparedusing the Mann-Whitney U test. Moreover, receiver-operating curve (ROC) analysis was applied to identify the cut-off values of SUVmax, MTV and TLG for the accurate differentiation of benign and malignant tumors. SUVmax, MTV and TLG were compared between thymomas and thymic carcinomas, as well as low-risk and high-risk thymomas.Results: Mean SUVmax, MTV and TLG of malignant mediastinal tumors were significantly higher compared to benign tumors (P

Objective(s): It is difficult to investigate the whole-body distribution of an orally administered drug by means of positron emission tomography (PET), owing to the short physical half-life of radionuclides, especially when 11C-labeled compounds are tested. Therefore, we aimed to examine the whole-body distribution of donepezil (DNP) as an acetylcholinesterase inhibitor by means of 11C-DNP PET imaging, combined with the oral administration of pharmacological doses of DNP.Methods: We studied 14 healthy volunteers, divided into group A (n=4) and group B (n=10). At first, we studied four females (mean age: 57.3±4.5 y), three of whom underwent 11C-DNP PET scan at 2.5 h after the oral administration of 1 mg and 30 μg of DNP, respectively, while one patient was scanned following the oral administration of 30 μg of DNP (group A). Then, we studied five females and five males (48.3±6.1 y), who underwent 11C-DNP PET scan, without the oral administration of DNP (group B). Plasma DNP concentration upon scanning was measured by tandem mass spectrometry. Arterialized venous blood samples were collected periodically to measure plasma radioactivity and metabolites. In group A, 11C-DNP PET scan of the brain and whole body continued for 60 and 20 min, respectively. Subjects in group B underwent sequential whole-body scan for 60 min. The regional uptake of 11C-DNP was analyzed by measuring the standard uptake value (SUV) through setting regions of interest on major organs with reference CT.Results: In group A, plasma DNP concentration was significantly correlated with the orally administered dose of DNP. The mean plasma concentration was 2.00 nM (n=3) after 1 mg oral administration and 0.06 nM (n=4) after 30 μg oral administration. No significant difference in plasma radioactivity or fraction of metabolites was found between groups A and B. High 11C-DNP accumulation was found in the liver, stomach, pancreas, brain, salivary glands, bone marrow, and myocardium in groups A and B, in this order. No significant difference in SUV value was found among 11C-DNP PET studies after the oral administration of 1 mg of DNP, 30 μg of DNP, or no DNP.Conclusion: The present study demonstrated that the whole-body distribution of DNP after the oral administration of pharmacological doses could be evaluated by 11C-DNP PET studies, combined with the oral administration of DNP.

Cerebral extraction of diffusively distributed substances like oxygen has been suggested to change according to the cerebral blood flow (CBF) and status of the microvasculature. The relationships between the cerebral extraction of diffusively distributed lipophilic tracers and the severity of cerebral ischemia has not yet been clarified. In the present study, we attempted to elucidate the association between the extraction fraction of the lipophilic tracer I-123 iomazenil (IMZ) (IMZ-EF) and the oxygen extraction fraction (OEF) derived from O-15 PET in patients with chronic steno-occlusive disease of internal carotid artery (ICA) or middle cerebral artery (MCA).Seven patients with unilateral chronic severe stenosis or occlusion of the middle cerebral/internal cerebral artery were prospectively recruited for this study. All the patients underwent both O-15 PET and quantitative I-123 IMZ SPECT. Parametric images derived from the PET and SPECT scans were anatomically normalized and evaluated by automated image analysis based on the volume-of-interest template.The asymmetry index (AI) of IMZ-EF was shown to be significantly correlated with the AI of OEF (r = 0.562, P < 0.001) in the internal carotid artery perfusion area. Strong and significant correlation between the AI of the influx rate constant K1 of IMZ and the AI of the cerebral metabolic rate of oxygen (r = 0.552, P = 0.001) was clarified.Our results suggested that the transportation efficiency of I-123 IMZ into the brain tissue was an indicator for evaluating severity of cerebral ischemia in patients with chronic steno-occlusive disease of ICA or MCA. Cerebral metabolic state can possibly be estimated by I-123 IMZ SPECT without cyclotron.

Objective(s): Post-treatment evaluations by CT/MRI (based on the International Working Group/ Cotswolds meeting guidelines) and PET (based on Revised Response Criteria), were examined in terms of progression-free survival (PFS) in patients with malignant lymphoma (ML). Methods: 79 patients, undergoing CT/MRI for the examination of suspected lesions and whole-body PET/CT before and after therapy, were included in the study during April 2007-January 2013. The relationship between post-treatment evaluations (CT/MRI and PET) and PFS during the follow-up period was examined, using Kaplan-Meier survival analysis. The patients were grouped according to the histological type into Hodgkin’s lymphoma (HL), diffuse large B-cell lymphoma (DLBCL), and other histological types. The association between post-treatment evaluations (PET or PET combined with CT/ MRI) and PFS was examined separately. Moreover, the relationship between disease recurrence and serum soluble interleukin-2 receptor, lactic dehydrogenase, and C-reactive protein levels was evaluated before and after the treatment. Results: Patients with incomplete remission on both CT/MRI and PET had a significantly shorter PFS, compared to patients with complete remission on both CT/MRI and PET and those exhibiting incomplete remission on CT/MRI and complete remission on PET (P

PURPOSE: Acetylcholinesterase (AChE) inhibitors have been used for patients with Alzheimer's disease. However, its pharmacokinetics in non-target organs other than the brain has not been clarified yet. The purpose of this study was to evaluate the relationship between the whole-body distribution of intravenously administered (11)C-Donepezil (DNP) and the AChE activity in the normal rat, with special focus on the adrenal glands. METHODS: The distribution of (11)C-DNP was investigated by PET/CT in 6 normal male Wistar rats (8 weeks old, body weight = 220 ± 8.9 g). A 30-min dynamic scan was started simultaneously with an intravenous bolus injection of (11)C-DNP (45.0 ± 10.7 MBq). The whole-body distribution of the (11)C-DNP PET was evaluated based on the Vt (total distribution volume) by Logan-plot analysis. A fluorometric assay was performed to quantify the AChE activity in homogenized tissue solutions of the major organs. RESULTS: The PET analysis using Vt showed that the adrenal glands had the 2nd highest level of (11)C-DNP in the body (following the liver) (13.33 ± 1.08 and 19.43 ± 1.29 ml/cm(3), respectively), indicating that the distribution of (11)C-DNP was the highest in the adrenal glands, except for that in the excretory organs. The AChE activity was the third highest in the adrenal glands (following the small intestine and the stomach) (24.9 ± 1.6, 83.1 ± 3.0, and 38.5 ± 8.1 mU/mg, respectively), indicating high activity of AChE in the adrenal glands. CONCLUSIONS: We demonstrated the whole-body distribution of (11)C-DNP by PET and the AChE activity in the major organs by fluorometric assay in the normal rat. High accumulation of (11)C-DNP was observed in the adrenal glands, which suggested the risk of enhanced cholinergic synaptic transmission by the use of AChE inhibitors.

Objective(s): This study aimed to evaluate the role of pretreatment SUVmax and volumetric FDG positron emission tomography (PET) parameters in the differentiation between benign and malignant mediastinal tumors. In addition, we investigated whether pretreatment SUVmax and volumetric FDG-PET parameters could distinguish thymomas from thymic carcinomas, and low-risk from high-risk thymomas. Methods: This study was conducted on 52 patients with mediastinal tumors undergoing FDG-PET/CT. Histological examination indicated that 29 mediastinal tumors were benign, and 23 cases were malignant. To obtain quantitative PET/CT parameters, we determined the maximum standardized uptake value (SUVmax), volumetric parameters, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for primary tumors using SUVmax cut-off value of 2.5. SUVmax, MTV and TLG of benign and malignant tumors were compared using the Mann-Whitney U test. Moreover, receiver-operating curve (ROC) analysis was applied to identify the cut-off values of SUVmax, MTV and TLG for the accurate differentiation of benign and malignant tumors. SUVmax, MTV and TLG were compared between thymomas and thymic carcinomas, as well as low-risk and high-risk thymomas. Results: Mean SUVmax, MTV and TLG of malignant mediastinal tumors were significantly higher compared to benign tumors (P<0.001). Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of SUVmax were 78.2%, 86.2%, 82.6%, 81.8%, and 83.3%, respectively. These values were estimated at 82.6%, 96.6%, 90.4%, 95%, and 87.5% for MTV and TLG, respectively. Additionally, optimal cut-off values for the differentiation of benign and malignant mediastinal tumors were determined at 4.2 and 22.3 mL and 79.7 g for SUVmax, MTV and TLG, respectively. Mean SUVmax, MTV and TLG of thymic carcinomas were significantly higher compared to thymomas (P<0.01), while no significant differences were observed in the mean quantitative parameters between low-risk and high-risk thymomas. Conclusion: Although SUVmax, MTV and TLG could not distinguish between low-risk and high-risk thymomas, these parameters might be able to differentiate benign tumors from malignant mediastinal tumors noninvasively. These parameters could be used to distinguish between thymomas and thymic carcinomas as well. Therefore, FDG-PET/CT parameters seem to be accurate indices for the detection of malignant mediastinal tumors. [ABSTRACT FROM AUTHOR]

Objective(s): It is difficult to investigate the whole-body distribution of an orally administered drug by means of positron emission tomography (PET), owing to the short physical half-life of radionuclides, especially when 11C-labeled compounds are tested. Therefore, we aimed to examine the whole-body distribution of donepezil (DNP) as an acetylcholinesterase inhibitor by means of 11C-DNP PET imaging, combined with the oral administration of pharmacological doses of DNP. Methods: We studied 14 healthy volunteers, divided into group A (n=4) and group B (n=10). At first, we studied four females (mean age: 57.3±4.5 y), three of whom underwent 11C-DNP PET scan at 2.5 h after the oral administration of 1 mg and 30 μg of DNP, respectively, while one patient was scanned following the oral administration of 30 μg of DNP (group A). Then, we studied five females and five males (48.3±6.1 y), who underwent 11C-DNP PET scan, without the oral administration of DNP (group B). Plasma DNP concentration upon scanning was measured by tandem mass spectrometry. Arterialized venous blood samples were collected periodically to measure plasma radioactivity and metabolites. In group A, 11C-DNP PET scan of the brain and whole body continued for 60 and 20 min, respectively. Subjects in group B underwent sequential whole-body scan for 60 min. The regional uptake of 11C-DNP was analyzed by measuring the standard uptake value (SUV) through setting regions of interest on major organs with reference CT. Results: In group A, plasma DNP concentration was significantly correlated with the orally administered dose of DNP. The mean plasma concentration was 2.00 nM (n=3) after 1 mg oral administration and 0.06 nM (n=4) after 30 μg oral administration. No significant difference in plasma radioactivity or fraction of metabolites was found between groups A and B. High 11C-DNP accumulation was found in the liver, stomach, pancreas, brain, salivary glands, bone marrow, and myocardium in groups A and B, in this order. No significant difference in SUV value was found among 11C-DNP PET studies after the oral administration of 1 mg of DNP, 30 μg of DNP, or no DNP. Conclusion: The present study demonstrated that the whole-body distribution of DNP after the oral administration of pharmacological doses could be evaluated by 11C-DNP PET studies, combined with the oral administration of DNP. [ABSTRACT FROM AUTHOR]