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Patients who undergo accelerator-based (AB) boron neutron capture therapy (BNCT) for head and neck cancer in the sitting position are generally uncomfortably immobilized, and patient motion during this treatment may be greater than that in other radiotherapy techniques. Furthermore, the treatment time of BNCT is relatively long (up to approximately 1 h), which increases the possibility of patient movement during treatment. As most BNCT irradiations are performed in a single fraction, the dosimetric error due to patient motion is of greater consequence and needs to be evaluated and accounted for. Several treatment parameters are required for BNCT dose calculation.To investigate the dosimetric impacts (DIs) against position errors using a simple cylindrical phantom for an AB-BNCT system under different treatment parameter settings.The treatment plans were created in RayStation and the dose calculation was performed using the NeuCure® dose engine. A cylindrical phantom (16 cm diameter × 20 cm height) made of soft tissue was modeled. Dummy tumors in the form of a 3-cm-diameter sphere were arranged at depths of 2.5 and 6.5 cm (denoted by TThe coefficients of the MRA of the DIs for LR, AP, and SI shifts were -0.08, 2.16, and -0.04 (p-values = 0.084, 0.01, and 0.334) for TThe DIs were largely affected by the shift in the AP direction and were influenced by the different treatment parameters.

This study was aimed at evaluating the metabolism of reactive astrocytes in the brains of patients with multiple sclerosis by quantitative 1-C-11 acetate positron emission tomography (PET). Magnetic resonance imaging and 1-C-11 quantitative PET were performed in eight patients with multiple sclerosis and 10 normal control subjects. The efflux rate (k2) of 1-C-11 acetate, which reportedly reflects the metabolic rate of 1-C-11 acetate, was calculated based on the one-tissue compartmental model. Fractional anisotropy was also determined to evaluate the integrity of the neuronal tracts. The values of k2 in the patients with multiple sclerosis were significantly higher than those in the normal control subjects, in both the white matter ( p = 0.003) and the gray matter ( p = 0.02). In addition, the white matter/gray matter ratio of k2 was significantly higher in the multiple sclerosis patients than in the normal control subjects ( p = 0.02). Voxel-based statistical analysis revealed most prominent increase in k2 in the neuronal fiber tracts, as well as decrease in fractional anisotropy in them in the multiple sclerosis patients. The present study clarified that the pathological changes associated with astrocytic reactivation in multiple sclerosis patients could be visualized by quantitative 1-C-11 acetate PET.

Objective Boron neutron capture therapy (BNCT) is a noninvasive radiation therapy method for cancer treatment. In BNCT, 4-borono-2-[18F]-fluoro-L-phenylalanine (18F-FBPA) PET has been employed to estimate 10B accumulation in target tumors and normal tissues if 10B borono-L-phenylalanine (10B-BPA) is used as a boron carrier. The purpose of the current study was to evaluate the total distribution volume (Vt) of 18F-FBPA in normal organs of healthy volunteers by kinetic analysis and to estimate boron concentration in normal organs for the therapeutic dose of 10B-BPA using obtained Vt values. Methods Six healthy volunteers were injected with 18F-FBPA (3–5 MBq/kg), and 7 PET-CT scans were performed subsequently. 18F-FBPA radioactivity in whole blood and plasma was measured before, and eight times after the injection. PET images were analyzed by PMOD software. Twelve volumetric regions of interest including the brain, heart, right lung, spleen, liver, parotid salivary glands, esophagus, stomach, pancreas, intestines, and bone marrow were drawn manually for each subject and analyzed with the Logan plot and two Ichise multilinear analyses (MA1 and MA2). The better model was defined by several goodness-of-fit parameters and residual distribution. After Vt values had been derived, boron concentration was estimated in ppm for the 10B-BPA-fructose (10B-BPA-fr) dose 30 g 1 and 2 h post-injection using Vt and interpolated plasma activity data. Results The Ichise MA2 model showed the best fit among all models. Akaike Information Criterion (AIC) was the lowest for the Ichise’s MA2 in all regions (mean AIC value − 14.0) comparing to the other models (Logan plot mean AIC 31.4; Ichise MA1 model mean AIC − 4.2). Mean Vt values of the Ichise MA2 model ranged from 0.94 ± 0.14 ml/ml in the pancreas to 0.16 ± 0.02 ml/ml in the right lung. Estimated boron concentration for 10B-BPA-fr had the highest value in the pancreas (14.0 ± 1.9 ppm 1 h after, and 5.7 ± 1.7 ppm 2 h after the 18F-FBPA administration) and the lowest value in the right lung (2.4 ± 0.3 ppm 1 h, and 1.0 ± 0.3 ppm 2 h post-injection). Conclusion The 10B concentration in normal tissues was best estimated using Vt values of 18F-FBPA with the Ichise multilinear analysis 2 (MA2). Trail registry The UMIN clinical trial number: UMIN000022850.

Salvage surgery after radiation therapy is known to be associated with a high incidence of postoperative complications. We describe a case of a successful salvage surgery after BNCT. In our patient with head and neck carcinoma, cervical lymph node recurrence with adhesion to a large vessel occurred after conventional radiotherapy. This lesion responded well to BNCT. Salvage surgery was subsequently performed to remove the residual tumor. Histopathologically, the isolated tissue contained tumor cells in its center and the surrounding tissue showed severe fibrosis. However, the tissue outside of the irradiation area had almost no fibrosis. BNCT may facilitate salvage surgery after radiotherapy because it causes less injury to the surrounding tissue than conventional radiotherapy. Our experience suggests that BNCT may be a feasible preoperative treatment in patients with inoperable lesions or in those who strongly desire preservation of function.

The purpose of this study was to determine if quantitative SUV-related, volumetric FDG PET parameters, and texture features (SPs, VPs, and TFs, respectively) were useful to evaluate and predict response and recurrence after chemotherapy in follicular lymphoma (FL). Pre- and posttreatment FDG PET examinations in 45 FL patients were analyzed retrospectively. In addition to SPs in the representative lesion, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated as VPs for the representative and whole-body lesions. Six TFs were calculated in the pretreatment representative lesion. Response results with reduction of SPs or VPs after treatment (Δ) were compared to the Lugano classification based on visual assessment. SPs, VPs, and Δ of them as well as TFs were also evaluated if they allow prediction of response and recurrence after chemotherapy. Quantitative assessment with SPs and VPs provided 89% and 93–96% concordant results, respectively, with Lugano classification. Among pretreatment PET parameters, low gray-level zone emphasis (LGZE) in TFs solely showed statistical significance to predict complete response. All of posttreatment and Δ of SPs and VPs were considered as the predictors of progression free survival in the univariate Cox regression analysis, but none of them was the predictor in the multivariate analysis. This study demonstrated that quantitative PET parameters were applicable to evaluate treatment response in FL. Texture analysis showed promise in predicting treatment response. Although posttreatment and Δ of PET parameters were the candidates, all of them proved to have limited value in predicting recurrence after chemotherapy.

Visual Abstract, Highlights • Intravenously injected ONO-1301–containing nanoparticles selectively accumulated in the ischemic border area of the myocardium. • Prominent up-regulation occurred of proangiogenic cytokines such as vascular endothelial growth factor and angiopoietin-1 in the ischemic myocardium, which may have contributed to the preservation of the native vascular and capillary networks, thus preserving regional myocardial blood flow. • Down-regulation of the proinflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α in the ischemic myocardium might have led to the attenuation of myocyte swelling and the suppression of the endothelial bleb formation, also contributing to the preservation of myocardial blood flow or the reduced infarct size., 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.

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.

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.

Carbon dioxide (CO2) treatment is reported to have an antitumor effect owing to the improvement in intratumoral hypoxia. Previous studies were based on histological analysis alone. In the present study, the improvement in intratumoral hypoxia by percutaneous CO2 treatment in vivo was determined using 18F-fluoromisonidazole positron emission tomography-computed tomography (18F-FMISO PET-CT) images. Twelve Japanese nude mice underwent implantation of LM8 tumor cells in the dorsal subcutaneous area 2 weeks before percutaneous CO2 treatment and 18F-FMISO PET-CT scans. Immediately after intravenous injection of 18F-FMISO, CO2 and room air were administered transcutaneously in the CO2-treated group (n=6) and a control group (n=6), respectively; each treatment was performed for 10 minutes. PET-CT was performed 2 h after administration of 18F-FMISO. 18F-FMISO tumor uptake was quantitatively evaluated using the maximum standardized uptake value (SUVmax), tumor-to-liver ratio (TLR), tumor-to-muscle ratio (TMR), metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Mean ± standard error of the mean (SEM) of the tumor volume was not significantly different between the two groups (CO2-treated group, 1.178±0.450 cm3; control group, 1.368±0.295 cm3; P=0.485). Mean ± SEM of SUVmax, TLR, MTV (cm3) and TLG were significantly lower in the CO2-treated group compared with the control group (0.880±0.095 vs. 1.253±0.071, P=0.015; 1.063±0.147361 vs. 1.455±0.078, P=0.041; 0.353±0.139 vs. 1.569±0.438, P=0.015; 0.182±0.070 vs. 1.028±0.338, P=0.015), respectively. TMR was not significantly different between the two groups (4.520±0.503 vs. 5.504±0.310; P=0.240). In conclusion, 18F-FMISO PET revealed that percutaneous CO2 treatment improved intratumoral hypoxia in vivo. This technique enables assessment of the therapeutic effect in CO2 treatment by imaging, and may contribute to its clinical application.

A previous study reported that a differential diagnosis between glioblastoma progression and radiation necrosis by 4-borono-2-[18F]-fluoro-phenylalanine ([18F]FBPA) PET can be made based on lesion-to-normal ratio of [18F]FBPA accumulation. Two-dimensional data acquisition mode PET alone system, with in-plane resolution of 7.9 mm and axial resolution of 13.9 mm, was used. In the current study, we aimed to confirm the differential diagnostic capability of [18F]FBPA PET/CT with higher PET spatial resolution by three-dimensional visual inspection and by measuring mean standardized uptake value (SUVmean), maximum SUV (SUVmax), metabolic tumor volume (MTV), and total lesion (TL) [18F]FBPA uptake. Twelve patients of glioma (9), malignant meningioma (1), hemangiopericytoma (1), and metastatic brain tumor (1) were enrolled. All had preceding radiotherapy. High-resolution three-dimensional data acquisition mode PET/CT with in-plane resolution of 4.07 mm and axial resolution of 5.41 mm was employed for imaging. Images were three-dimensionally analyzed using the PMOD software. SUVmean and SUVmax of lesion and normal brain were measured. Lesion MTV and TL FBPA uptake were calculated. The diagnostic accuracy of [18F]FBPA PET/CT in detecting recurrence (n = 6) or necrosis (n = 6) was verified by clinical follow-up. All parameters showed significantly higher values for tumor recurrence than for necrosis. SUVmean in recurrence was 2.95 ± 0.84 vs 1.18 ± 0.24 in necrosis (P = 0.014); SUVmax in recurrence was 4.63 ± 1.23 vs 1.93 ± 0.44 in necrosis (P = 0.014); MTV in recurrence was 44.92 ± 28.93 mL vs 10.66 ± 8.46 mL in necrosis (P = 0.032); and mean TL FBPA uptake in recurrence was 121.01 ± 50.48 g vs 12.36 ± 9.70 g in necrosis (P = 0.0029). In this preliminary feasibility study, we confirmed the possibility of differentiating tumor recurrence from radiation necrosis in patients with irradiated brain tumors by [18F]FBPA PET/CT using indices of SUVmean, SUVmax, MTV, and TL 18FBPA uptake.

Resting-state functional MRI (rs-fMRI) has revealed the existence of a default-mode network (DMN) based on spontaneous oscillations of the blood oxygenation level-dependent (BOLD) signal. The BOLD signal reflects the deoxyhemoglobin concentration, which depends on the relationship between the regional cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO2). However, these two factors cannot be separated in BOLD rs-fMRI. In this study, we attempted to estimate the functional correlations in the DMN by means of quantitative 15O-labeled gases and water PET, and to compare the contribution of the CBF and CMRO2 to the DMN. Nine healthy volunteers (5 men and 4 women; mean age, 47.0 ± 1.2 years) were studied by means of 15O-O2, 15O-CO gases and 15O-water PET. Quantitative CBF and CMRO2 images were generated by an autoradiographic method and transformed into MNI standardized brain template. Regions of interest were placed on normalized PET images according to the previous rs-fMRI study. For the functional correlation analysis, the intersubject Pearson’s correlation coefficients (r) were calculated for all pairs in the brain regions and correlation matrices were obtained for CBF and CMRO2, respectively. We defined r > 0.7 as a significant positive correlation and compared the correlation matrices of CBF and CMRO2. Significant positive correlations (r > 0.7) were observed in 24 pairs of brain regions for the CBF and 22 pairs of brain regions for the CMRO2. Among them, 12 overlapping networks were observed between CBF and CMRO2. Correlation analysis of CBF led to the detection of more brain networks as compared to that of CMRO2, indicating that the CBF can capture the state of the spontaneous activity with a higher sensitivity. We estimated the functional correlations in the DMN by means of quantitative PET using 15O-labeled gases and water. The correlation matrix derived from the CBF revealed a larger number of brain networks as compared to that derived from the CMRO2, indicating that contribution to the functional correlation in the DMN is higher in the blood flow more than the oxygen consumption.

This study aimed to compare the tumor volume definition using conventional magnetic resonance (MR) and 11C-methionine positron emission tomography (MET/PET) images in the differentiation of the pre-operative glioma grade by using whole-tumor histogram analysis of normalized cerebral blood volume (nCBV) maps. Thirty-four patients with histopathologically proven primary brain low-grade gliomas (n = 15) and high-grade gliomas (n = 19) underwent pre-operative or pre-biopsy MET/PET, fluid-attenuated inversion recovery, dynamic susceptibility contrast perfusion-weighted magnetic resonance imaging, and contrast-enhanced T1-weighted at 3.0 T. The histogram distribution derived from the nCBV maps was obtained by co-registering the whole tumor volume delineated on conventional MR or MET/PET images, and eight histogram parameters were assessed. The mean nCBV value had the highest AUC value (0.906) based on MET/PET images. Diagnostic accuracy significantly improved when the tumor volume was measured from MET/PET images compared with conventional MR images for the parameters of mean, 50th, and 75th percentile nCBV value (p = 0.0246, 0.0223, and 0.0150, respectively). Whole-tumor histogram analysis of CBV map provides more valuable histogram parameters and increases diagnostic accuracy in the differentiation of pre-operative cerebral gliomas when the tumor volume is derived from MET/PET images.

Generally, FDG-PET/CT image is acquired at the 60th minute after tracer administration. Depending on the clinical case, additional delayed scans may be useful. However, it is difficult to judge whether additional delayed scan is useful or not. The purposes of this study were creation and evaluation of educational programs to help radiological technologists to decide the usefulness of additional delayed scan of FDG-PET/CT. METHODS Educational programs consisted of the instructional materials and the judgment test of clinical cases. The instructional materials provided the valuable findings for differentiation between uptake in the wall of the colon and colon content, distinction between uptake in the lymph node and urinary tract, and evaluation of malignancy. The judgment test of clinical cases consisted of 10 cases selected by a nuclear medicine physician (for 5 of that cases additional delayed scan was decided to be useful). Five experienced technologists and five inexperienced technologists scored the volubility of additional delayed scan pre- and post-training using the instructional materials (the full marks of score is 5). RESULTS After the educational programs using the instructional materials, the score was improved with the significant difference in both experienced (pre: 3.6±1.4, post: 4.0±1.2) and inexperienced (pre: 2.8±1.5, post: 3.7±1.5) groups (p

Objective Boron neutron capture therapy (BNCT) is a noninvasive radiation therapy method for cancer treatment. In BNCT, 4-borono-2-[18F]-fluoro-L-phenylalanine (18F-FBPA) PET has been employed to estimate 10B accumulation in target tumors and normal tissues if 10B borono-L-phenylalanine (10B-BPA) is used as a boron carrier. The purpose of the current study was to evaluate the total distribution volume (Vt) of 18F-FBPA in normal organs of healthy volunteers by kinetic analysis and to estimate boron concentration in normal organs for the therapeutic dose of 10B-BPA using obtained Vt values. Methods Six healthy volunteers were injected with 18F-FBPA (3–5 MBq/kg), and 7 PET-CT scans were performed subsequently. 18F-FBPA radioactivity in whole blood and plasma was measured before, and eight times after the injection. PET images were analyzed by PMOD software. Twelve volumetric regions of interest including the brain, heart, right lung, spleen, liver, parotid salivary glands, esophagus, stomach, pancreas, intestines, and bone marrow were drawn manually for each subject and analyzed with the Logan plot and two Ichise multilinear analyses (MA1 and MA2). The better model was defined by several goodness-of-fit parameters and residual distribution. After Vt values had been derived, boron concentration was estimated in ppm for the 10B-BPA-fructose (10B-BPA-fr) dose 30 g 1 and 2 h post-injection using Vt and interpolated plasma activity data. Results The Ichise MA2 model showed the best fit among all models. Akaike Information Criterion (AIC) was the lowest for the Ichise’s MA2 in all regions (mean AIC value − 14.0) comparing to the other models (Logan plot mean AIC 31.4; Ichise MA1 model mean AIC − 4.2). Mean Vt values of the Ichise MA2 model ranged from 0.94 ± 0.14 ml/ml in the pancreas to 0.16 ± 0.02 ml/ml in the right lung. Estimated boron concentration for 10B-BPA-fr had the highest value in the pancreas (14.0 ± 1.9 ppm 1 h after, and 5.7 ± 1.7 ppm 2 h after the 18F-FBPA administration) and the lowest value in the right lung (2.4 ± 0.3 ppm 1 h, and 1.0 ± 0.3 ppm 2 h post-injection). Conclusion The 10B concentration in normal tissues was best estimated using Vt values of 18F-FBPA with the Ichise multilinear analysis 2 (MA2). Trail registry The UMIN clinical trial number: UMIN000022850. Electronic supplementary material The online version of this article (10.1007/s12149-019-01427-9) contains supplementary material, which is available to authorized users.

Occlusion of a major coronary artery induces myocardial infarction (MI), leading to left ventricle (LV) remodeling due to progressive microvasculature dysfunction. Irreversible impairment in microvascular function has been suggested to extend from the infarcted region into the infarct-border or remote regions, depending on the time to revascularization. Our aim was to determine whether the occlusion of a major coronary artery induces microvascular dysfunction in the adjacent area perfused by intact coronary arteries using a porcine model for chronic total occlusion of the left anterior descending artery (LAD). MI was induced via an ameroid constrictor ring around the LAD in adult Gottingen pigs (Sus scrofa domesticus, n = 5). Age-matched normal pigs were treated as controls (n = 3). Cardiac magnetic resonance showed reduced systolic regional wall motion in the left circumflex (LCx) and right coronary artery (RCA) territories, with a progressively worsening motion in the infarction-adjacent area over an eight-week period. On 13N-ammonia positron emission tomography (PET), myocardial blood flow (MBF) during hyperemia was significantly greater in the LCx and RCA territories (particularly in the infarction-adjacent area) compared to that in the LAD territory at four weeks after infarct induction. Subsequently, the flow significantly decreased, approaching that in the LAD territory at eight weeks after infarct induction. Fluoroscopy-guided pressure-wire studies showed significantly higher microvascular resistance in the LCx area at eight weeks compared to that in controls. Electron microscopy showed endothelium swelling and microvasculature disruption in areas adjacent to the LCx and RCA territories. Anterior MI caused coronary microvascular dysfunction in the adjacent area, associated with a reduced MBF and regional wall motion.

In boron neutron capture therapy (BNCT) for cancer, the accurate estimation of 10B tissue concentrations, especially in neighboring normal organs, is important to avoid adverse effects. The 10B concentration in normal organs after loading with 10B, however, has not been established in humans. In this study, we performed 4-borono-2-[18F]-fluoro-phenylalanine (18FBPA) PET in healthy volunteers and estimated the chronological changes in the 10B concentrations of normal organs. In 6 healthy volunteers, whole-body 18FBPA PET scans were repeated 7 times during 1 h, and the mean 18FBPA distributions of 13 organs were measured. Based on the 18FBPA PET data, we then estimated the changes in the 10B concentrations of the organs when the injection of a therapeutic dose of 10BPA–fructose complex (10BPA–fr; 30 g, 500 mg/kg body weight) was assumed. The maximum mean 18FBPA concentrations were reached at 2–6 min after injection in all the organs except the brain and urinary bladder. The mean 18FBPA concentration in normal brain plateaued at 24 min after injection. When the injection of a therapeutic dose of 10BPA–fr was assumed, the estimated mean 10B concentration in the kidney increased to 126.1 ± 24.2 ppm at 3 min after injection and then rapidly decreased to 30.9 ± 7.4 ppm at 53 min. The estimated mean 10B concentration in the bladder gradually increased and reached 383.6 ± 214.7 ppm at 51 min. The mean 10B concentration in the brain was estimated to be 7.6 ± 1.5 ppm at 57 min. 18FBPA PET has a potential to estimate 10B concentration of normal organs before neutron irradiation of BNCT when several assumptions are validated in the future studies.

We have applied boron neutron capture therapy (BNCT) for 46 recurrent high grade meningiomas (HGM). Twelve cases among them, fluoride-labeled boronophenylalanine positron emission tomography (18F-BPA-PET) were utilized before and after BNCT to evaluate the tumor activity. The lesion to normal brain (L/N) ratios of 14 lesions of these 11 cases were investigated. In all cases L/N ratio decreased after BNCT. The L/N ratio of recurrent (HGM) was 3.2±1.5 (mean±SD) before BNCT and 2.1±0.6 after that. In contrast enhanced MRI, 13 out of 14 lesions shrank or unchanged at least 3 months after BNCT, while one lesion transiently increased and then decreased within 3 months, showing pseudoprogression. In addition, 6 of 12 lesions which could be followed on MRI for more than 3 months progressed after 8 months. 4 of them were performed PET at the time of progressing. The L/N ratio of 2 progressing lesion which were diagnosed as recurrence due to continuously increasing were showed increasing. The L/N ratio of the other 2 lesions which were diagnosed radiation necrosis due to unchanged or shrinkage showed decreasing. Moreover, some systemic metastasis detected in PET image. F-BPA-PET seems to be useful for the evaluation of tumor activity.

It has become evident that positron emission tomography/computed tomography (PET-CT) using 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) (FDG PET-CT) can detect anti-tumor immune response induced by various immunotherapies. To evaluate whether FDG PET-CT could detect anti-cancer immune response caused by cancer vaccine therapy, we performed a retrospective analysis of FDG PET-CT imaging of patients who were treated with Wilms Tumor 1 (WT1) vaccine therapy in Osaka University during July 2008 and June 2018. Increased FDG uptakes were detected in WT1-vaccinated skin and their draining lymph nodes during the repeated vaccination. While the FDG uptakes seemed to decrease with time after the cessation of WT1 peptide vaccinations, persistence of FDG uptakes for years in WT1-vaccinated skin were also observed in 2 cases who showed good clinical course. Moreover, the FDG uptakes of patients treated with the combination vaccine of WT1 specific cytotoxic T cell (CTL) and helper peptides were significantly stronger than of those treated with the WT1 CTL peptide alone. Since it is evident that the combination vaccine can induce a more robust anti-tumor immunity than can CTL peptide vaccine alone, the FDG uptakes in WT1-vaccinated skin might reflect the degree of immune response. These results suggest that PET-CT might be a good tool for prediction of anti-tumor immune response induced by WT1 vaccine therapy. Larger scale prospective studies therefore seem to be warranted.

Boron neutron capture therapy (BNCT) is the particle irradiation therapy that the selective radiation for tumor cells is available for theoretically. The role that the amino acid (phenylalanine) PET (18F-BPA-PET) that we used boronophenylalanine (BPA) which is a boron compound for neutron capture reaction as a tracer carries out is major in our BNCT especially for the recent non-craniotomy BNCT, and it covers by treatment, observation from indication. In this report, we introduce this PET as a principal axis about BNCT and a relation of the PET.In our BNCT, we calculated the drug accumulation to the tumor from BPA-PET before neutron irradiation and reflected it for individual treatment. We become able to decide indication of BNCT by using this PET study, and the indication expansion to other systemic cancers including head and neck cancer and lung, liver is now worked on actively. Also, in other irradiation modalities, they make a radiation plan based on PET study, and several reports to try the improvement of results had been present, however, high radiation doses will be “ exposed “ to the lesion showing high accumulation in BPA-PET in BNCT. We determine the neutron exposure time from the dosage for the normal tissue in the actual treatment, but the Lesion / Normal tissue ratio obtained from BPA-PET is reflected by the evaluation of the tumor dose and the following treatment plan. Also, after the treatment, diagnoses of the pathologic condition such as an increase in tumor volume, a recurrence or the radiation necrosis might be difficult, and we found that the PET study was useful in the follow-up stage for the patients with already treated malignant brain tumor.

A previous study reported that a differential diagnosis between glioblastoma progression and radiation necrosis by 4-borono-2-[Twelve patients of glioma (9), malignant meningioma (1), hemangiopericytoma (1), and metastatic brain tumor (1) were enrolled. All had preceding radiotherapy. High-resolution three-dimensional data acquisition mode PET/CT with in-plane resolution of 4.07 mm and axial resolution of 5.41 mm was employed for imaging. Images were three-dimensionally analyzed using the PMOD software. SUVmean and SUVmax of lesion and normal brain were measured. Lesion MTV and TL FBPA uptake were calculated. The diagnostic accuracy of [All parameters showed significantly higher values for tumor recurrence than for necrosis. SUVmean in recurrence was 2.95 ± 0.84 vs 1.18 ± 0.24 in necrosis (P = 0.014); SUVmax in recurrence was 4.63 ± 1.23 vs 1.93 ± 0.44 in necrosis (P = 0.014); MTV in recurrence was 44.92 ± 28.93 mL vs 10.66 ± 8.46 mL in necrosis (P = 0.032); and mean TL FBPA uptake in recurrence was 121.01 ± 50.48 g vs 12.36 ± 9.70 g in necrosis (P = 0.0029).In this preliminary feasibility study, we confirmed the possibility of differentiating tumor recurrence from radiation necrosis in patients with irradiated brain tumors by [

Objective Resting-state functional MRI (rs-fMRI) has revealed the existence of a default-mode network (DMN) based on spontaneous oscillations of the blood oxygenation level-dependent (BOLD) signal. The BOLD signal reflects the deoxyhemoglobin concentration, which depends on the relationship between the regional cerebral blood flow (CBF) and the cerebral metabolic rate of oxygen (CMRO2). However, these two factors cannot be separated in BOLD rs-fMRI. In this study, we attempted to estimate the functional correlations in the DMN by means of quantitative 15O-labeled gases and water PET, and to compare the contribution of the CBF and CMRO2 to the DMN. Methods Nine healthy volunteers (5 men and 4 women; mean age, 47.0 ± 1.2 years) were studied by means of 15O-O2, 15O-CO gases and 15O-water PET. Quantitative CBF and CMRO2 images were generated by an autoradiographic method and transformed into MNI standardized brain template. Regions of interest were placed on normalized PET images according to the previous rs-fMRI study. For the functional correlation analysis, the intersubject Pearson’s correlation coefficients (r) were calculated for all pairs in the brain regions and correlation matrices were obtained for CBF and CMRO2, respectively. We defined r > 0.7 as a significant positive correlation and compared the correlation matrices of CBF and CMRO2. Results Significant positive correlations (r > 0.7) were observed in 24 pairs of brain regions for the CBF and 22 pairs of brain regions for the CMRO2. Among them, 12 overlapping networks were observed between CBF and CMRO2. Correlation analysis of CBF led to the detection of more brain networks as compared to that of CMRO2, indicating that the CBF can capture the state of the spontaneous activity with a higher sensitivity. Conclusions We estimated the functional correlations in the DMN by means of quantitative PET using 15O-labeled gases and water. The correlation matrix derived from the CBF revealed a larger number of brain networks as compared to that derived from the CMRO2, indicating that contribution to the functional correlation in the DMN is higher in the blood flow more than the oxygen consumption.

Non-Hodgkin's lymphoma (NHL) cases with inconclusive biopsy findings are not infrequently referred for fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (Retrospectively, 328 patients were selected by the following inclusion criteria: biopsy-proven NHL with no more than one histopathological type; new cases with less than 90 days between obtaining biopsy andThe SUVmax of NHL tends to be higher in TOFBoth SUVmax10g/mL in non-TOF

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. Electronic supplementary material The online version of this article (10.1186/s13550-017-0335-7) contains supplementary material, which is available to authorized users.

Objective We hypothesized that therapeutic efficacy may be augmented by a combination of placing a sheet immersed in ONO-1301SR, a slow-release synthetic prostacyclin agonist-inducing multiproangiogenic cytokines, over the left ventricle and a pedicled omental flap in a chronic myocardial infarct heart. Methods A minipig chronic myocardial infarction was generated by placing an ameroid constrictor ring around the left anterior descending artery for 4 weeks. The minipigs were then assigned into 4 groups of 6 each: sham, omental flap only, ONO-1301SR only, and ONO-1301SR combined with an omental flap (combined). Four weeks after treatment, therapeutic efficacy was evaluated histologically and via several modalities used in the clinical setting. Results In an angiogram and pressure wire study, the combined group induced development of collateral arteries to decrease the resistance and increase the flow reserve of microvasculature in the left circumflex territory. In a 13 N-ammonia positron emission tomography study, the combined group displayed a prominent increase in myocardial blood flow and myocardial flow reserve in the left circumflex territory, particularly at the infarct-border region. Consequently, the combined group showed greater regional cardiac function in the left circumflex territory particularly at the infarct-border region, contributing to a greater global ejection fraction with a smaller left ventricular endosystolic volume. Pathologically, attenuated fibrosis, nonswollen myocytes, and upgraded capillary density and proangiogenic cytokines were prominent in the combined group. Conclusions ONO-1301SR combined with a pedicled omental flap synergistically promoted myocardial angiogenesis, leading to function recovery in a porcine chronic myocardial infarction model.

Background 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). Methods 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. Results 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. Conclusions 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.

Schema of the tube connection for the 15O-gas supply. Figure S2. Workflow for image reconstruction and data analysis. Figure S3. Relationship between the radioactivity of 15O-gas flow and the radioactivity concentration in the lung. Figure S4. Percent change in the radioactivity concentration against FBP (**Pâ

Multiple VOI settings on coronal fusion image of 18F-FMISO PET (window level 0–3 in SUV) and TBF PET (window level 0–80 ml/100 mL/min). VOIs (1-mm sphere) were manually placed over the entire tumor where there is an uptake of 18F-FMISO or TBF on the fusion PET images. Figure S2. Relationships between the 18F-FMISO SUV and quantitative values of TBF, TMRO2, OEF, and TBV of each tumor. Decreased trend of TBF and TBV, increased trend of OEF, and stable TMRO2 against the increase of 18F-FMISO SUV were observed. (DOC 673 kb)

Background Intratumoral hypoxia is one of the resistant factors in radiotherapy and chemotherapy for cancer. Although it is detected by 18F-fluoromisonidazole (FMISO) PET, the relationship between intratumoral hypoxia and oxygen metabolism has not been studied. The purpose of this study was to evaluate the intratumoral perfusion and oxygen metabolism in hypoxic regions using the rat xenograft model. Ten male Fischer rats with C6 glioma (body weight = 220 ± 15 g) were investigated with 18F-FMISO PET and steady-state inhalation method of 15O-labelled gases PET. The tumoral blood flow (TBF), tumoral metabolic rate of oxygen (TMRO2), oxygen extraction fraction (OEF), and tumoral blood volume (TBV) were measured under artificial ventilation with 15O–CO2, 15O–O2, and 15O–CO gases. Multiple volumes of interest (1-mm diameter sphere) were placed on the co-registered 18F-FMISO (3 h post injection) and functional 15O-labelled gases PET images. The TBF, TMRO2, OEF, and TBV values were compared among the three groups classified by the 18F-FMISO uptake as follows: group Low (L), less than 1.0; group Medium (M), between 1.0 and 2.0; and group High (H), more than 2.0 in the 18F-FMISO standardized uptake value (SUV). Results There were moderate negative correlations between 18F-FMISO SUV and TBF (r = −0.56 and p

Background In boron neutron capture therapy (BNCT), positron emission tomography (PET) with 4-borono-2-18F-fluoro-phenylalanine (FBPA) is the only method to estimate an accumulation of 10B to target tumor and surrounding normal tissue after administering 10B carrier of L-paraboronophenylalanine and to search the indication of BNCT for individual patient. Absolute concentration of 10B in tumor has been estimated by multiplying 10B concentration in blood during BNCT by tumor to blood radioactivity (T/B) ratio derived from FBPA PET. However, the method to measure blood radioactivity either by blood sampling or image data has not been standardized. We compared image-derived blood radioactivity of FBPA with blood sampling data and studied appropriate timing and location for measuring image-derived blood counts. Methods We obtained 7 repeated whole-body PET scans in five healthy subjects. Arterialized venous blood samples were obtained from the antecubital vein, heated in a heating blanket. Time-activity curves (TACs) of image-derived blood radioactivity were obtained using volumes of interest (VOIs) over ascending aorta, aortic arch, pulmonary artery, left and right ventricles, inferior vena cava, and abdominal aorta. Image-derived blood radioactivity was compared with those measured by blood sampling data in each location. Results Both the TACs of blood sampling radioactivity in each subject, and the TACs of image-derived blood radioactivity showed a peak within 5 min after the tracer injection, and promptly decreased soon thereafter. Linear relationship was found between blood sampling radioactivity and image-derived blood radioactivity in all the VOIs at any timing of data sampling (p

In boron neutron capture therapy (BNCT) for cancer, the accurate estimation ofIn 6 healthy volunteers, whole-bodyThe maximum mean

The linear correlation between (11)C-methionine PET and tumor cell density is not well conserved at the tumor border in glioma. A novel imaging analysis method, voxelwise (18)F-FDG-(11)C-methionine PET decoupling analysis (decoupling score), was evaluated to determine whether it could be used to quantitatively assess glioma cell infiltration in MRI-nonenhancing T2 hyperintense lesions.Data collection was performed in a prospective fashion. Fifty-four MRI-nonenhancing T2 hyperintense specimens were stereotactically obtained from 23 glioma patients by intraoperative navigation guidance. The decoupling score and tumor-to-normal tissue (T/N) ratio of (11)C-methionine PET were calculated at each location. Correlations between the tumor cell density at these lesions, decoupling score, and T/N ratio of (11)C-methionine PET were then evaluated.Both the decoupling score and the T/N ratio showed a linear correlation with tumor cell density at these specimens (R(2) = 0.52 and 0.53, respectively). Use of the decoupling score (cutoff = 3.0) allowed the detection of specimens with a tumor cell density of more than 1,000/mm(2), with a sensitivity and specificity of 93.5% and 87.5%, respectively, whereas conventional (11)C-methionine PET (cutoff = 1.2 in T/N ratio) was able to detect with a sensitivity and specificity of 87.0% and 87.5%, respectively. Reconstructed images (decoupling map) using the decoupling score enabled the visualization of glioma lesions that were difficult to visualize by (11)C-methionine PET alone.The decoupling score showed better performance in detecting glioma cell infiltration than (11)C-methionine uptake alone, thus suggesting that (18)F-FDG-(11)C-methionine uptake decoupling analysis is a powerful imaging modality for assessing glioma invasion.

BACKGROUND AND PURPOSE: It has been suggested, on the basis of a previous pilot study conducted in a small number of patients, that MR imaging–based PVE correction in I-123 iomazenil brain SPECT improves the detectability of cortical epileptogenic foci. In the present study, we performed an investigation by using a larger sample size to establish the effectiveness of the PVE correction and to conduct a detailed evaluation based on the histologic classification of lesions. MATERIALS AND METHODS: Seventy-five patients (male/female, 37/38; age, 28 ± 12 years) with intractable epilepsy who had undergone surgical treatment were enrolled in this study. I-123 iomazenil SPECT and MR imaging examinations were performed before the operation in all patients. I-123 iomazenil SPECT images with and without MR imaging–based PVE correction were assessed visually and by semiquantitative analysis based on the AI(%) of the SPECT count in the resected lesions. RESULTS: The sensitivity, specificity, and accuracy of foci detection by visual assessment were significantly higher after PVE correction compared with the values obtained before the correction. The results of the semiquantitative analysis revealed that the asymmetry of the SPECT counts was significantly increased after the PVE correction in the surgically resected lesions in cases of mesial temporal sclerosis, tumor, and malformations of cortical development. CONCLUSIONS: The effectiveness of MR imaging–based PVE correction in I-123 iomazenil brain SPECT in improving the detection of cortical epileptogenic foci with abnormal histologic findings was established by our investigation conducted on a large sample size.

Recently, PET response criteria in solid tumors (PERCIST) have been proposed as a new standardized method to assess chemotherapeutic response metabolically and quantitatively. The aim of this study was to evaluate therapeutic response to neoadjuvant chemotherapy for locally advanced esophageal cancer, comparing PERCIST with the currently widely used response evaluation criteria in solid tumors (RECIST).Fifty-one patients with locally advanced esophageal cancer who received neoadjuvant chemotherapy (5-fluorouracil, adriamycin, and cisplatin), followed by surgery were studied. Chemotherapeutic lesion responses were evaluated using (18)F-FDG PET and CT according to the RECIST and PERCIST methods. The PET/CT scans were obtained before chemotherapy and about 2 wk after completion of chemotherapy. Associations were statistically analyzed between survival (overall and disease-free survival) and clinicopathologic results (histology [well-, moderately, and poorly differentiated squamous cell carcinoma], lymphatic invasion, venous invasion, clinical stage, pathologic stage, resection level, reduction rate of tumor diameter, reduction rate of tumor uptake, chemotherapeutic responses in RECIST and PERCIST, and pathologic response).There was a significant difference in response classification between RECIST and PERCIST (Wilcoxon signed-rank test, P0.0001). Univariate analysis showed that lymphatic invasion, venous invasion, resection level, pathologic stage, and PERCIST were significant factors associated with disease-free or overall survival in this study. Although multivariate analysis demonstrated that venous invasion (disease-free survival: hazard ratio [HR] = 4.519, P = 0.002; overall survival: HR = 5.591, P = 0.003) and resection level (disease-free survival: HR = 11.078, P = 0.001) were the significant predictors, PERCIST was also significant in noninvasive therapy response assessment before surgery (disease-free survival: HR = 4.060, P = 0.025; overall survival: HR = 8.953, P = 0.034).RECIST based on the anatomic size reduction rate did not demonstrate the correlation between therapeutic responses and prognosis in patients with esophageal cancer receiving neoadjuvant chemotherapy. However, PERCIST was found to be the strongest independent predictor of outcomes. Given the significance of noninvasive radiologic imaging in formulating clinical treatment strategies, PERCIST might be considered more suitable for evaluation of chemotherapeutic response to esophageal cancer than RECIST.

Object Immunotherapy targeting the Wilms tumor 1 (WT1) gene product is a promising treatment modality for patients with malignant gliomas, and there have been reports of encouraging results. It has become clear, however, that Gd-enhanced MR imaging does not reflect prognosis, thereby necessitating a more robust imaging evaluation system for monitoring response to WT1 immunotherapy. To meet this demand, the authors performed a voxel-wise parametric response map (PRM) analysis of 11C-methionine PET (MET-PET) in WT1 immunotherapy and compared the data with the overall survival after initiation of WT1 immunotherapy (OSWT1). Methods Fourteen patients with recurrent malignant glioma were included in the study, and OSWT1 was compared with: 1) volume and length change in the contrast area of the tumor on Gd-enhanced MR images; 2) change in maximum uptake of 11C-methionine; and 3) a more detailed voxel-wise PRM analysis of MET-PET pre- and post-WT1 immunotherapy. Results The PRM analysis was able to identify the following 3 areas within the tumor core: 1) area with no change in 11C-methionine uptake pre- and posttreatment; 2) area with increased 11C-methionine uptake posttreatment (PRM+MET); and 3) area with decreased 11C-methionine uptake posttreatment. While the results of Gd-enhanced MR imaging volumetric and conventional MET-PET analysis did not correlate with OSWT1 (p = 0.270 for Gd-enhanced MR imaging length, p = 0.960 for Gd-enhanced MR imaging volume, and p = 0.110 for MET-PET), the percentage of PRM+MET area showed excellent correlation (p = 0.008) with OSWT1. Conclusions This study describes the limited value of Gd-enhanced MR imaging and highlights the potential of voxel-wise PRM analysis of MET-PET for monitoring treatment response in immunotherapy for malignant gliomas. Clinical trial registration no.: UMIN000002001.

BACKGROUND AND PURPOSE: CBR imaging is highly susceptible to a PVE produced by morphologic changes in the brain related to aging and brain laterality. We assessed the influence of PVE produced by regional age-related changes in gray matter volume on I-123 iomazenil SPECT and elucidated the age-related changes in human CBR binding by using PVE-corrected SPECT images. MATERIALS AND METHODS: Nineteen right-handed healthy volunteers (range, 25–82 years; mean, 55 ± 21 years) underwent MR imaging and quantitative I-123 iomazenil SPECT imaging. The influence of age-related changes in rGMC on SPECT images before PVE correction was assessed. PVE correction of the SPECT images was performed by using an MR imaging–based method. Voxel-based linear regression analyses of the PVE-corrected SPECT images were performed by using SPM5. RESULTS: The age-related reductions in rGMC and BP without PVE correction revealed a significant direct proportional correlation. Voxel-based statistical analysis with PVE correction showed no significant age-related changes in BP. CONCLUSIONS: PVE correction was indispensable for the analysis of I-123 iomazenil SPECT images. PVE-corrected quantitative I-123 iomazenil SPECT images revealed no age-related changes in CBR binding in right-handed healthy humans.