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Purpose: To investigate within phantoms the minimum CT dose allowed for accurate attenuation correction of PET data and to quantify the effective dose reduction when a CT for this purpose is incorporated in the clinical setting. Methods: The NEMA image quality phantom was scanned within a large parallelepiped container. Twenty-one different CT images were acquired to correct attenuation of PET raw data. Radiation dose and image quality were evaluated. Thirty-one patients with proven multiple myeloma who underwent a dual tracer PET/CT scan were retrospec- tively reviewed. 18F-fluorodeoxyglucose PET/CT included a diagnostic whole-body low dose CT (WBLDCT: 120 kV-80mAs) and 11C-Methionine PET/CT included a whole-body ultra-low dose CT (WBULDCT) for attenuation correction (100 kV-40mAs). Effective dose and image quality were analysed. Results: Only the two lowest radiation dose conditions (80 kV-20mAs and 80 kV-10mAs) produced artifacts in CT images that degraded corrected PET images. For all the other conditions (CTDIvol ≥ 0.43 mGy), PET contrast recovery coefficients varied less than ± 1.2%. Patients received a median dose of 6.4 mSv from diagnostic CT and 2.1 mSv from the attenuation correction CT. Despite the worse image quality of this CT, 94.8% of bone lesions were identifiable. Conclusion: Phantom experiments showed that an ultra-low dose CT can be implemented in PET/CT procedures without any noticeable degradation in the attenuation corrected PET scan. The replacement of the standard CT for this ultra-low dose CT in clinical PET/CT scans involves a significant radiation dose reduction

Volume changes induced by selective internal radiation therapy (SIRT) may increase the possibility of tumor resection in patients with insufficient future liver remnant (FLR). The aim was to identify dosimetric and clinical parameters associated with contralateral hepatic hypertrophy after lobar/extended lobar SIRT with 90Y-resin microspheres. Patients underwent 90Y PET/CT after lobar or extended lobar (right + segment IV) SIRT. 90Y voxel dosimetry was retrospectively performed (PLANET Dose; DOSIsoft SA). Mean absorbed doses to tumoral/non-tumoral-treated volumes (NTL) and dose-volume histograms were extracted. Clinical variables were collected. Patients were stratified by FLR at baseline (T0-FLR): < 30% (would require hypertrophy) and ≥ 30%. Changes in volume of the treated, non-treated liver, and FLR were calculated at < 2 (T1), 2–5 (T2), and 6–12 months (T3) post-SIRT. Univariable and multivariable regression analyses were performed to identify predictors of atrophy, hypertrophy, and increase in FLR. The best cut-off value to predict an increase of FLR to ≥ 40% was defined using ROC analysis. Fifty-six patients were studied; most had primary liver tumors (71.4%), 40.4% had cirrhosis, and 39.3% had been previously treated with chemotherapy. FLR in patients with T0-FLR < 30% increased progressively (T0: 25.2%; T1: 32.7%; T2: 38.1%; T3: 44.7%). No dosimetric parameter predicted atrophy. Both NTL-Dmean and NTL-V30 (fraction of NTL exposed to ≥ 30 Gy) were predictive of increase in FLR in patients with T0 FLR < 30%, the latter also in the total cohort of patients. Hypertrophy was not significantly associated with tumor dose or tumor size. When ≥ 49% of NTL received ≥ 30 Gy, FLR increased to ≥ 40% (accuracy: 76.4% in all patients and 80.95% in T0-FLR < 30% patients). NTL-Dmean and NTL exposed to ≥ 30 Gy (NTL-V30) were most significantly associated with increase in FLR (particularly among patients with T0-FLR < 30%). When half of NTL received ≥ 30 Gy, FLR increased to ≥ 40%, with higher accuracy among patients with T0-FLR < 30%.

Radioembolization (RE) with yttrium-90 (90Y) microspheres, a transcatheter intraarterial therapy for patients with liver cancer, can be modeled computationally. The purpose of this work was to correlate the results obtained with this methodology using in vivo data, so that this computational tool could be used for the optimization of the RE procedure. The hepatic artery three-dimensional (3D) hemodynamics and microsphere distribution during RE were modeled for six 90Y-loaded microsphere infusions in three patients with hepatocellular carcinoma using a commercially available computational fluid dynamics (CFD) software package. The model was built based on in vivo data acquired during the pretreatment stage. The results of the simulations were compared with the in vivo distribution assessed by 90Y PET/CT. Specifically, the microsphere distribution predicted was compared with the actual 90Y activity per liver segment with a commercially available 3D-voxel dosimetry software (PLANET Dose, DOSIsoft). The average difference between the CFD-based and the PET/CT-based activity distribution was 2.36 percentage points for Patient 1, 3.51 percentage points for Patient 2 and 2.02 percentage points for Patient 3. These results suggest that CFD simulations may help to predict 90Y-microsphere distribution after RE and could be used to optimize the RE procedure on a patient-specific basis.

It remains unclear whether the supportive imaging features described in the diagnostic criteria for progressive supranuclear palsy (PSP) are suitable for the full clinical spectrum. The aim of the current study was to define and cross-validate the pattern of glucose metabolism in the brain associated with a diagnosis of different PSP variants. A retrospective multicenter cohort study performed on 73 PSP patients who were referred for a fluorodeoxyglucose positron emission tomography PET scan: PSP-Richardson's syndrome, n = 47; PSP-parkinsonian variant, n = 18; and progressive gait freezing, n = 8. In addition, we included 55 healthy controls and 58 Parkinson's disease (PD) patients. Scans were normalized by global mean activity. We analyzed the regional differences in metabolism between the groups. Moreover, we applied a multivariate analysis to obtain a PSP-related pattern that was cross-validated in independent populations at the individual level. Group analysis showed relative hypometabolism in the midbrain, basal ganglia, thalamus, and frontoinsular cortices and hypermetabolism in the cerebellum and sensorimotor cortices in PSP patients compared with healthy controls and PD patients, the latter with more severe involvement in the basal ganglia and occipital cortices. The PSP-related pattern obtained confirmed the regions described above. At the individual level, the PSP-related pattern showed optimal diagnostic accuracy to distinguish between PSP and healthy controls (sensitivity, 80.4%; specificity, 96.9%)s and between PSP and PD (sensitivity, 80.4%; specificity, 90.7%). Moreover, PSP-Richardson's syndrome and PSP-parkinsonian variant patients showed significantly more PSP-related pattern expression than PD patients and healthy controls. The glucose metabolism assessed by fluorodeoxyglucose PET is a useful and reproducible supportive diagnostic tool for PSP-Richardson's syndrome and PSP-parkinsonian variant. © 2020 International Parkinson and Movement Disorder Society.

Primary schools contribute to promoting healthy eating behaviour and preventing overweight and obesity by providing nutrition education. Research highlights the importance of improving teachers’ programme implementation to enhance intervention effectiveness. An integrative approach has been suggested to reduce time barriers that teachers currently experience in teaching nutrition. This scoping review explores use and effectiveness of integrative teaching in primary-school-based nutrition education programmes. Six databases were searched for primary-school-based interventions on nutrition education. Papers reporting on integration of nutrition topics within core curriculum were included. Abstracts and full texts of potentially relevant articles were screened to determine eligibility. Next, data were extracted and tabulated. Findings were collated and summarised to describe intervention characteristics, subject integration and effectiveness of the included programmes. Data describing integration of nutrition into the primary school curriculum were extracted from 39 eligible papers. Nutrition education programmes often involve lessons about food groups and are frequently embedded within the mathematics, science or literacy syllabus. Although articles report on the integration of nutrition, the use of this approach was not commonly described in detail. Only seven papers discussed student outcomes related to the integration of nutrition education within core subjects. The ability to draw strong conclusions about school-based nutrition intervention effectiveness is limited by the current lack of programme description and methodological issues. Hence, more research is warranted to inform evidence on effectiveness of integrative nutrition education for both teacher and student outcomes. Future studies that include greater detail regarding the integrative approach are needed.

Therapeutic options for cancer patients have increased in the last years, although drugs resistance problem remains unresolved. Genetic background in individual susceptibility to cancer treatment could influence the therapy responses. The aim of this study was to explore the feasibility of using blood 4 genes (AEG-1, BRCA-1, REV3L and TYMS) expression levels as a predictor of the efficacy of pemetrexed therapy in patients with advanced non-small cell lung cancer. Sixteen patients from the Medical Oncology Department at “12 de Octubre” Hospital, were included in the study. Total mRNA was isolated from blood samples, and gene expression was analyzed by RT-qPCR. A panel of lung tumor cell lines were used in cell proliferation tests and siRNA-mediated silencing assays. Similarity between blood gene expression levels and protein expression in matched tumor tissue was observed in 54.54% (REV3L) and 81.81% (TYMS) of cases. Gene expression of REV3L and TYMS in blood correlated directly and inversely, respectively, with progression-free survival and overall survival in the patients from our cohort. In tumor cell lines, the knockdown of REV3L conferred resistance to pemetrexed treatment, and the TYMS silencing increased the pemetrexed sensitivity of tumor cells. The use of peripheral blood samples for expression quantification of interest genes is an affordable method with promising results in the evaluation of response to pemetrexed treatment. Therefore, expression levels of REV3L and TYMS genes might be used as predictive biomarkers in advanced NSCLC patients.

BackgroundTo facilitate population screening and clinical trials of disease-modifying therapies for Alzheimer’s disease, supportive biomarker information is necessary. This study was aimed to investigate the association of plasma amyloid-beta (Aβ) levels with the presence of pathological accumulation of Aβ in the brain measured by amyloid-PET. Both plasma Aβ42/40 ratio alone or combined with an FDG-PET-based biomarker of neurodegeneration were assessed as potential AD biomarkers.MethodsWe included 39 cognitively normal subjects and 20 patients with mild cognitive impairment from the AB255 Study who had undergone PiB-PET scans. Total Aβ40 and Aβ42 levels in plasma (TP42/40) were quantified using ABtest kits. Subjects were dichotomized as Aβ-PET positive or negative, and the ability of TP42/40 to detect Aβ-PET positivity was assessed by logistic regression and receiver operating characteristic analyses. Combination of plasma Aβ biomarkers and FDG-PET was further assessed as an improvement for brain amyloidosis detection and diagnosis classification.ResultsEighteen (30.5%) subjects were Aβ-PET positive. TP42/40 ratio alone identified Aβ-PET status with an area under the curve (AUC) of 0.881 (95% confidence interval [CI] = 0.779–0.982). Discriminating performance of TP42/40 to detect Aβ-PET-positive subjects yielded sensitivity and specificity values at Youden’s cutoff of 77.8% and 87.5%, respectively, with a positive predictive value of 0.732 and negative predictive value of 0.900. All these parameters improved after adjusting the model for significant covariates. Applying TP42/40 as the first screening tool in a sequential diagnostic work-up would reduce the number of Aβ-PET scans by 64%. Combination of both FDG-PET scores and plasma Aβ biomarkers was found to be the most accurate Aβ-PET predictor, with an AUC of 0.965 (95% CI = 0.913–0.100).ConclusionsPlasma TP42/40 ratio showed a relevant and significant potential as a screening tool to identify brain Aβ positivity in preclinical and prodromal stages of Alzheimer’s disease.

One key feature of pancreatic ductal adenocarcinoma (PDAC) is a dense desmoplastic reaction that has been recognized as playing important roles in metastasis and therapeutic resistance. We aim to study tumor–stromal interactions in an in vitro coculture model between human PDAC cells (Capan-1 or PL-45) and fibroblasts (LC5). Confocal immunofluorescence, Enzyme-Linked Immunosorbent Assay (ELISA), and Western blotting were used to evaluate the expressions of activation markers, cytokines arrays were performed to identify secretome profiles associated with migratory and invasive properties of tumor cells, extracellular vesicle production was examined by ELISA and transmission electron microscopy. Coculture conditions increased FGF-7 secretion and α-SMA expression, characterized by fibroblast activation and decreased epithelial marker E-cadherin in tumor cells. Interestingly, tumor cells and fibroblasts migrate together, with tumor cells in forming a center surrounded by fibroblasts, maximizing the contact between cells. We show a different mechanism for tumor spread through a cooperative migration between tumor cells and activated fibroblasts. Furthermore, IL-6 levels change significantly in coculture conditions, and this could affect the invasive and migratory capacities of cells. Targeting the interaction between tumor cells and the tumor microenvironment might represent a novel therapeutic approach to advanced PDAC.

Background: Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancer worldwide. One key feature of PDAC is a dense desmoplastic reaction that has become recognized to play important roles in tumor growth, metastasis, and therapeutic resistance. We aim to study tumor-stromal interactions in an in vitro co-culture model between human PDAC cells and fibroblasts.Methods: Capan-1 or PL-45 human pancreatic tumor cell lines and LC5 fibroblasts were grown in direct or indirect co-cultures, and their relationship regarding migratory and invasive properties were studied by wound-healing and transwell migration assays. Confocal immunofluorescence, ELISA, and western blotting were used to evaluate the expression of activation markers. Cytokines arrays were performed to identify secretome profiles associated to migratory and invasive properties of tumor cells. Extracellular vesicles production was examined by ELISA and transmission electron microscopy. Results: Co-cultures conditions increased FGF-7 secretion and α-SMA expression, characterizing fibroblasts activation; and decreased epithelial marker E-cadherin in tumor cells, suggesting that they suffer epithelial-to-mesenchymal transition. The expression pattern of cytokine secretion differed under co-culture conditions versus monocultures, with GM-CSF, GRO a/b/g, GRO-α, IL-6, IL-8, MCP-1, and RANTES being the most affected. A greater number of exosomes with higher amount of proteins was quantified in co-cultures assays. Interestingly, tumor cells and fibroblasts migrate as a package, with tumor cells in the middle surrounded by fibroblasts, and maximizing the contact between cell to cell. Conclusions: We show different migratory properties in tumor and stromal cells, and we draw a different mechanism for tumor spread through a cooperative migration between tumor cells and activated fibroblasts. Furthermore, we found that the level of IL-6 mainly, in addition to other cytokines, change significantly in co-cultures conditions with respect to monocultures, and this could affect the invasive and migratory capacities of cells. Targeting the interaction between tumor cells and tumor microenvironment might represent a novel therapeutic approach to advance pancreatic carcinoma.

Background Nutrition education programs in schools have been effective in improving children’s knowledge and behaviours related to food and nutrition. However, teachers find it challenging to implement such programs due to overcrowded curricula. Integrating nutrition with core subjects such as mathematics could potentially address time constraints and improve the learning of both. The primary aim of this randomized controlled trial (RCT) is to evaluate the impact of a cross-curricular nutrition and mathematics program on primary school students’ portion size estimation skills. Secondary aims include impact on their nutrition knowledge, attitudes towards mathematics and evaluating the quality of the lessons. Methods Twelve Year 3–4 classes from Catholic schools in New South Wales, Australia will be randomised to intervention (n = 6) or control (n = 6) groups. Teachers in the intervention group will receive a professional development workshop and resources to teach 4–5 lessons on portion size and measurements across 1–4 weeks. Outcome measures include portion size estimation skills, nutrition knowledge and attitudes towards mathematics, with data collected during three school visits (pre-intervention, immediately post-intervention, 4 weeks post-intervention). Additionally, teaching quality will be assessed in both intervention and control groups and process evaluation undertaken using teacher interviews and student focus groups. Discussion This RCT uses an innovative approach to improve both nutrition and mathematics related learning outcomes among primary school children. It has the potential to impact teaching practices regarding integration of nutrition into curricula and enhance the implementation of nutrition education interventions. Trial registration Australian and New Zealand Clinical Trials Register ACTRN12619001071112 31/07/2019.

Brain positron emission tomography imaging with 18Fluorine-fluorodeoxyglucose (FDG-PET) has demonstrated utility in suspected autoimmune encephalitis. Visual and/or assisted image reading is not well established to evaluate hypometabolism/hypermetabolism. We retrospectively evaluated patients with autoimmune encephalitis between 2003 and 2018. Patients underwent EEG, brain magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) sampling and autoantibodies testing. Individual FDG-PET images were evaluated by standard visual reading and assisted by voxel-based analyses, compared to a normal database. For the latter, three different methods were performed: two based on statistical surface projections (Siemens syngo.via Database Comparison, and 3D-SSP Neurostat) and one based on statistical parametric mapping (SPM12). Hypometabolic and hypermetabolic findings were grouped to identify specific patterns. We found six cases with definite diagnosis of autoimmune encephalitis. Two cases had anti-LGI1, one had anti-NMDA-R and two anti-CASPR2 antibodies, and one was seronegative. 18F-FDG-PET metabolic abnormalities were present in all cases, regardless of the method of analysis. Medial–temporal and extra-limbic hypermetabolism were more clearly depicted by voxel-based analyses. We found autoantibody-specific patterns in line with the literature. Statistical surface projection (SSP) methods (Neurostat and syngo.via Database Comparison) were more sensitive and localized larger hypermetabolic areas. As it may lead to comparable and accurate results, visual analysis of FDG-PET studies for the diagnosis of autoimmune encephalitis benefits from voxel-based analysis, beyond the approach based on MRI, CSF sample and EEG.

11C-methionine (11C-MET) is a new positron emission tomography (PET) tracer for the assessment of disease activity in multiple myeloma (MM) patients, with preliminary data suggesting higher sensitivity and specificity than 18F-fluorodeoxyglucose (18F-FDG). However, the value of tumor burden biomarkers has yet to be investigated. Our goals were to corroborate the superiority of 11C-MET for MM staging and to compare its suitability for the assessment of metabolic tumor burden biomarkers in comparison to 18F-FDG. Twenty-two patients with newly diagnosed, treatment-na&iuml, ve symptomatic MM who had undergone 11C-MET and 18F-FDG PET/CT were evaluated. Standardized uptake values (SUV) were determined and compared with total metabolic tumor volume (TMTV) for both tracers: total lesion glycolysis (TLG) and total lesion 11C-MET uptake (TLMU). PET-derived values were compared to Revised International Staging System (R-ISS), cytogenetic, and serologic MM markers such as M component, beta 2 microglobulin (B2M), serum free light chains (FLC), albumin, and lactate dehydrogenase (LDH). In 11 patients (50%), 11C-MET detected more focal lesions (FL) than FDG (p &lt, 0.01). SUVmax, SUVmean, SUVpeak, TMTV, and TLMU were also significantly higher in 11C-MET than in 18F-FDG (p &lt, 0.05, respectively). 11C-MET PET biomarkers had a better correlation with tumor burden (bone marrow plasma cell infiltration, M component, p &lt, 0.05 versus p = n.s. respectively). This pilot study suggests that 11C-MET PET/CT is a more sensitive marker for the assessment of myeloma tumor burden than 18F-FDG. Its implications for prognosis evaluation need further investigation.

Background Prior radioembolization, a simulation using 99mTc-macroaggregated albumin as 90Y-microspheres surrogate is performed. Gamma scintigraphy images (planar, SPECT, or SPECT-CT) are acquired to evaluate intrahepatic 90Y-microspheres distribution and detect possible extrahepatic and lung shunting. These images may be used for pre-treatment dosimetry evaluation to calculate the 90Y activity that would get an optimal tumor response while sparing healthy tissues. Several dosimetry methods are available, but there is still no consensus on the best methodology to calculate absorbed doses. The goal of this study was to retrospectively evaluate the impact of using different dosimetry approaches on the resulting 90Y-radioembolization pre-treatment absorbed dose evaluation based on 99mTc-MAA images. Methods Absorbed doses within volumes of interest resulting from partition model (PM) and 3D voxel dosimetry methods (3D-VDM) (dose-point kernel convolution and local deposition method) were evaluated. Additionally, a new “Multi-tumor Partition Model” (MTPM) was developed. The differences among dosimetry approaches were evaluated in terms of mean absorbed dose and dose volume histograms within the volumes of interest. Results Differences in mean absorbed dose among dosimetry methods are higher in tumor volumes than in non-tumoral ones. The differences between MTPM and both 3D-VDM were substantially lower than those observed between PM and any 3D-VDM. A poor correlation and concordance were found between PM and the other studied dosimetry approaches. DVH obtained from either 3D-VDM are pretty similar in both healthy liver and individual tumors. Although no relevant global differences, in terms of absorbed dose in Gy, between both 3D-VDM were found, important voxel-by-voxel differences have been observed. Conclusions Significant differences among the studied dosimetry approaches for 90Y-radioembolization treatments exist. Differences do not yield a substantial impact in treatment planning for healthy tissue but they do for tumoral liver. An individual segmentation and evaluation of the tumors is essential. In patients with multiple tumors, the application of PM is not optimal and the 3D-VDM or the new MTPM are suggested instead. If a 3D-VDM method is not available, MTPM is the best option. Furthermore, both 3D-VDM approaches may be indistinctly used.

Aims To present four examples of clonally related Epstein-Barr virus (EBV)-associated large-cell transformation of marginal zone lymphoma (MZL) (of nodal, extranodal and splenic types), occurring 120, 11 and 5 months after the initial diagnosis in three instances, and concurrently in one case; and to discuss several interesting features of EBV infection. Methods and results Somatic mutations were detected by use of a customised panel for next-generation sequencing and polymerase chain reaction studies of IgH in both low-grade and high-grade components of each case. In case 1, the initial biopsy of nodal MZL showed scattered EBV-positive cells, which might constitute an indication of EBV-induced progression. Case 2 showed heterogeneous EBV expression, a phenomenon attributable to loss of the EBV episomes during cell division, or to a secondary superinfection or reactivation of the virus. In case 3, p53 overexpression related to gene mutation and EBV-encoded small RNAs were identified in the same neoplastic component. In case 4, the mucosa-associated lymphoid tissue-type MZL and the high-grade component were identified concurrently in a patient previously treated with methotrexate for an autoimmune disorder. Conclusion These data suggest that the presence of EBV should be added to the list of potential markers to be analysed for MZL prognosis.

Background Cachexia is a metabolic syndrome that affects up to 50-80% of cancer patients. The pathophysiology is characterized by a variable combination of reduced food intake and abnormal metabolism, including systemic inflammation and negative protein and energy balance. Despite its high clinical significance, defined diagnostic criteria and established therapeutic strategies are lacking. The 'omics' technologies provide a global view of biological systems. We hypothesize that blood-based metabolomics might identify findings in cachectic patients that could provide clues to gain knowledge on its pathophysiology, and eventually postulate new therapeutic strategies. Methods This is a cross-sectional observational study in two cohorts of cancer patients, with and without cachexia. Patients were consecutively recruited from routine clinical practice of a General Oncology Department at '12 de Octubre' University Hospital. Selected clinical and biochemical features were collected. Blood metabolite fingerprinting was performed using three analytical platforms, gas chromatography coupled to mass spectrometry (GC-MS), capillary electrophoresis coupled to mass spectrometry (CE-MS), and liquid chromatography coupled to mass spectrometry (LC-MS). Besides, we performed pathway-based metabolite analyses to obtain more information on biological functions. Results A total of 15 subjects were included in this study, 8 cachectic and 7 non-cachectic patients. Metabolomic analyses were able to correctly classify their samples in 80% (GC-MS), 97% (CE-MS), 96% [LC-MS (positive mode)], and 89% [LC-MS (negative mode)] of the cases. The most prominent metabolic alteration in plasma of cachectic patients was the decrease of amino acids and derivatives [especially arginine, tryptophan, indolelactic acid, and threonine, with 0.4-fold change (FC) compared with non-cachectic patients], along with the reduction of glycerophospholipids [mainly lysophosphatidylcholines(O-16:0) and lysophosphatidylcholines(20:3) sn-1, FC = 0.1] and sphingolipids [SM(d30:0), FC = 0.5]. The metabolite with the highest increase was cortisol (FC = 1.6). Such alterations suggest a role of the following metabolic pathways in the pathophysiology of cancer cachexia: arginine and proline metabolism; alanine, aspartate, and glutamate metabolism; phenylalanine metabolism; lysine degradation; aminoacyl-tRNA biosynthesis; fatty acid elongation in mitochondria; tricarboxylic acids cycle; among others. Conclusions These findings suggest that plasma amino acids and lipids profiling has great potential to find the mechanisms involved in the pathogenesis of cachexia. Metabolic profiling of plasma from cancer patients show differences between cachexia and non-cachexia in amino acids and lipids that might be related to mechanisms involved in its pathophysiology. A better understanding of these mechanisms might identify novel therapeutic approaches to palliate this unmet medical condition.

To reduce the radiation dose to patients by optimizing oncological FDG PET/CT protocols.The baseline PET/CT protocol in our institution for oncological PET/CT examinations consisted of the administration of 5.18 MBq/kg of FDG and a CT acquisition with a reference current-time product of 120 mAs. In 2016, FDG activity was reduced to 4.44 and 3.70 MBq/kg and reference CT current-time-product was reduced to 100 and 80 mAs. 322 patients scanned with different protocols were retrospectively evaluated. For each patient, effective dose was calculated. The overall image quality was subjectively rated by the referring physician on a 4-point scale (IQ score: 1 excellent, 2 good, 3 poor but interpretable, 4 poor not interpretable). Image quality was quantitatively evaluated measuring noise in the liver.CT Results: Effective dose was progressively reduced from 9.5 ± 2.8 to 8.0 ± 2.3 and 6.2 ± 1.5 mSv (p 0.001). A mean dose reduction of 34.9% was achieved. There was a significant degradation of IQ score (p 0.05) and noise (p 0.001). Nevertheless, the number of poor quality studies (IQ score2) did not increase. PET Results: Effective dose was gradually reduced from 6.5 ± 1.4 to 5.7 ± 1.3 and 5.0 ± 1.0 mSv (p 0.001). Average dose reduction was 23.4%. IQ score (p 0.05) and noise (p 0.001) significantly degraded for lower activity protocols. However, all images with reduced activity were scored as interpretable (IQ score ≤ 3).A significant radiation dose reduction of 28.7% was reached. Despite a slight reduction in image quality, the new regime was successfully implemented with readers reporting unchanged clinical confidence.

Background: Heavily pretreated relapsed and refractory multiple myeloma (RR MM) constitutes a specific and unmet medical need. Median survival ranges from as little as 6 to 9 months, and responses to treatment are characteristically short (Richardson et al. 2007). Belantamab Mafodotin (BM), a novel anti-BCMA antibody conjugated to microtubule-disrupting agent monomethyl auristatin F, showed single-agent activity in the phase 1 DREAMM-1 and phase 2 DREAMM-2 studies in heavily pre-treated patients with RRMM (Lonial et al, 2019 & 2021). We aim to assess efficacy and safety of BM treatment administered via the expanded access compassionate care program for triple class MMRR patients in the region of Madrid (Spain). Methods: An observational, retrospective and multicenter study has been performed including all patients who received at least one dose of BM under the expanded access program in the region of Madrid (Spain) from Nov 2019 to Jun 2021. Hematology centers provided data from the medical records and entered them in a case report form distributed to the sites. Primary endpoint was overall response rate (ORR). Secondary endpoints were progression free survival (PFS), overall survival (OS) and the incidence of treatment emergent adverse events (TEAEs), with a major focus on ocular and hematologic toxicity. Results: A total of 33 patients (pts), from 14 different centers, were included from February 2020 till May 2021. Median age was 70 (46-79) years. 55% of the pts were women. Median time from diagnosis was 71 (10-858) months. 30.3% were high-risk cytogenetic features. Median of prior therapy lines was 5 (3-8) and at least 88% of the pts were triple class refractory. The median number of BM doses per patient was 3 (1-16) and the median follow-up was 11 months (95%CI 6.34-15.66). ORR was 42.2%, and 18.2% achieved ≥VGPR. Median PFS was 3 months (95%CI 0.92-5.08). Median PFS for patients who achieved ≥PR was 11 months (HR 0,26; 95% CI 0,10-0,68). No significant differences were found in PFS according to age, cytogenetic risk and prior therapy lines. OS was 424 days (95% CI 107-740). The incidence of non-hematological TEAEs was 57.6% and the most common of which was ocular toxicity (45.5%). The incidence of ≥G3 non-hematological TEAEs was 30.3%. 51.5% of the pts were diagnosed of keratopathy and 21.2% was ≥G3. 30.3% of the pts showed a reduced visual acuity, but this event was resolved in 92.9% of the pts. The most common symptoms were blurry vision (30.3%, n=10) and dry eye (24.2%, n=8). The incidence of ≥G3 hematological TEAEs was 18.2% and thrombocytopenia was the most frequent (21.2%). Dose reductions of BM were required in 30.3% of the pts and delayed in 36.4% due to TEAEs. Main causes for treatment discontinuation (81%, n=27) were disease progression (54.5%, n=18), toxicity (15.2%, n=5), death (6.1%, n=3) and due to patient's decision (3%, n=1). Conclusion: Compassionate use of BM in heavily pretreated RR MM pts showed a relevant anti-myeloma activity with a manageable safety profile.These results are similar to those observed in the DREAMM-1 and DREAMM-2 clinical trials. Disclosures No relevant conflicts of interest to declare.

Our aim was to evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) fused with prone 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in primary tumour staging of patients with breast cancer.This retrospective study evaluated 45 women with 49 pathologically proven breast carcinomas. MRI and prone PET-CT scans with time-of-flight and point-spread-function reconstruction were performed with the same dedicated breast coil. The studies were assessed by a radiologist and a nuclear medicine physician, and evaluation of fused images was made by consensus. The final diagnosis was based on pathology (90 lesions) or follow-up ≥ 24 months (17 lesions).The study assessed 72 malignant and 35 benign lesions with a median size of 1.8 cm (range 0.3-8.4 cm): 31 focal, nine multifocal and nine multicentric cases. In lesion-by-lesion analysis, sensitivity, specificity, positive and negative predictive values were 97%, 80%, 91% and 93% for MRI, 96%, 71%, 87%, and 89% for prone PET, and 97%. 94%, 97% and 94% for MRI fused with PET. Areas under the curve (AUC) were 0.953, 0.850, and 0.983, respectively (p 0.01).MRI fused with FDG-PET is more accurate than FDG-PET in primary tumour staging of breast cancer patients and increases the specificity of MRI.• FDG PET-CT may improve the specificity of MRI in breast cancer staging. • MRI fused with prone 2-[fluorine-18]-fluoro-2-deoxy-D-glucose PET-CT has better overall diagnostic performance than MRI. • The clinical role of fused PET-MRI has not yet been established.

Objectives The aim of this study was to assess the dose received by members of the public due to close contact with patients undergoing nuclear medicine procedures during radiopharmaceutical incorporation, and comparing it with the emitted radiation dose when the test was complete, in order to establish recommendations. Material and methods A prospective study was conducted on 194 patients. H*(10) dose rates were measured at 0.1, 0.5, and 1.0 m after the radiopharmaceutical administration, before the image acquisition, and at the end of the nuclear medicine procedure. Effective dose for different close contact scenarios were calculated, according to 95th percentile value (bone scans) and the maximum value (remaining tests). Results During the radiopharmaceutical incorporation, a person who stays with another injected patient in the same waiting room may receive up to 0.59 mSv. If the patient had a medical appointment, or went to a restaurant or a coffee shop, members of the public could receive 23, 43, and 22 μSv, respectively. After finishing the procedure, these doses are reduced by a factor 3. In most of the studies, the use of private instead of public transport may reduce the dose by more than a factor 6. Conclusion It is recommended to increase the distance between the patients during the radiopharmaceutical incorporation and to distribute them according to the diagnostic procedure. Patients should be encouraged to use private instead of public transport. Depending on the number of nuclear medicine outpatients per year attended by a physician, it could be necessary to apply restrictions.

Background The uveitis masquerade syndromes (UMS) are a group of ocular diseases that may mimic chronic intraocular inflammation. Many malignant entities such as non-Hodgkin's lymphomas may masquerade as uveitis. We report a case of an HIV-positive patient with masquerade syndrome presenting unilateral uveitis. Case report 45-year-old Caucasian man with a diagnosis of diffuse large B-cell lymphoma (DLBCL). The patient was diagnosed by a biopsy of an abdominal mass which showed fragments of gastric mucosa with diffuse growth of neoplastic cells. At diagnosis, the patient suffered from unilateral blurring of vision and a sudden decrease of left-eye visual acuity. A slit-lamp examination of the left eye revealed a diagnosis of anterior uveitis. The patient exhibited no signs of posterior uveitis. An anterior-chamber paracentesis was performed and analyzed by multiparameter flow cytometry (MFC), showing cells CD45, CD19, CD20, CD22, and CD38 positives, and moderate expression of CD10 with kappa light chain restriction, showing a monoclonal B-cell population. The patient received CHOP-R with intrathecal methotrexate followed by consolidation high dose methotrexate obtaining a complete response which is ongoing. Conclusion Differential diagnosis between chronic uveitis and ocular lymphoma may be challenging. We advocate anterior-chamber paracentesis in cases of refractory uveitis in patients with hematologic malignancies. © 2016 International Clinical Cytometry Society.

Clinical diagnosis of human prion diseases can be challenging since symptoms are common to other disorders associated with rapidly progressive dementia. In this context, 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) might be a useful complementary tool. The aim of this study was to determine the metabolic pattern in human prion diseases, particularly sporadic Creutzfeldt-Jakob disease (sCJD), the new variant of Creutzfeldt-Jakob disease (vCJD) and fatal familial insomnia (FFI). We retrospectively studied 17 patients with a definitive, probable or possible prion disease who underwent FDG PET in our institution. Of these patients, 12 were diagnosed as sCJD (9 definitive, 2 probable and 1 possible), 1 was diagnosed as definitive vCJD and 4 were diagnosed as definitive FFI. The hypometabolic pattern of each individual and comparisons across the groups of subjects (control subjects, sCJD and FFI) were evaluated using a voxel-based analysis. The sCJD group exhibited a pattern of hypometabolism that affected both subcortical (bilateral caudate, thalamus) and cortical (frontal cortex) structures, while the FFI group only presented a slight hypometabolism in the thalamus. Individual analysis demonstrated a considerable variability of metabolic patterns among patients, with the thalamus and basal ganglia the most frequently affected areas, combined in some cases with frontal and temporal hypometabolism. Patients with a prion disease exhibit a characteristic pattern of brain metabolism presentation in FDG PET imaging. Consequently, in patients with rapidly progressive cognitive impairment, the detection of these patterns in the FDG PET study could orient the diagnosis to a prion disease.

This article presents an analysis of the impact of functional neuroimaging studies (positron emission tomography, PET) in asymmetric hearing loss based on the clinical expertise obtained from a group of 21 patients. In these patients, PET studies are performed at rest and after auditory stimulation in order to measure the increase in brain activity in the ipsi- and contralateral cortex, providing supporting evidence to recommend a specific treatment and the side to implant. In conclusion, PET is a useful tool for selected cases in which information on the metabolic status of the auditory pathway can drive the decision regarding the treatment of the most appropriate ear. However, in view of our small sample, further research is needed to confirm our results in this topic.

Background In 2014, Siemens developed a new software-based scatter correction (Progressive Reconstruction Intelligently Minimizing Exposure [PRIME]), enabling grid-less digital mammography. Purpose To compare doses and image quality between PRIME (grid-less) and standard (with anti-scatter grid) modes. Material and Methods Contrast-to-noise ratio (CNR) was measured for various polymethylmethacrylate (PMMA) thicknesses and dose values provided by the mammograph were recorded. CDMAM phantom images were acquired for various PMMA thicknesses and inverse Image Quality Figure (IQFinv) was calculated. Values of incident entrance surface air kerma (ESAK) and average glandular dose (AGD) were obtained from the DICOM header for a total of 1088 pairs of clinical cases. Two experienced radiologists compared subjectively the image quality of a total of 149 pairs of clinical cases. Results CNR values were higher and doses were lower in PRIME mode for all thicknesses. IQFinv values in PRIME mode were lower for all thicknesses except for 40 mm of PMMA equivalent, in which IQFinv was slightly greater in PRIME mode. A mean reduction of 10% in ESAK and 12% in AGD in PRIME mode with respect to standard mode was obtained. The clinical image quality in PRIME and standard acquisitions resulted to be similar in most of the cases (84% for the first radiologist and 67% for the second one). Conclusion The use of PRIME software reduces, in average, the dose of radiation to the breast without affecting image quality. This reduction is greater for thinner and denser breasts.

The epithelial-to-mesenchymal transition (EMT) is a biological process in which a non-motile epithelial cell changes to a mesenchymal state with invasive capacities. However, the EMT program is involved in both physiological and pathological processes. Cancer-associated EMT is known to contribute to increase invasiveness and metastasis, resistance to therapies, and generation of cell populations with stem cell-like characteristics and therefore is deeply involved in tumor progression. This process is finely orchestrated by multiple signaling pathways and regulatory transcriptional networks. The hallmark of EMT is the loss of epithelial surface markers, mainly E-cadherin, and the acquisition of mesenchymal phenotype. These events can be mediated by EMT transcription factors which can cooperate with several enzymes to repress the E-cadherin expression and regulate EMT at the epigenetic and post-translational level. A growing body of evidence indicates that cancer cells can reside in various phenotypic states along the EMT spectrum, where cells can jointly retain epithelial traits with mesenchymal ones. This type of phenotypic plasticity endows cancer cells with tumor-initiating potential. The identification of the signaling pathways and modulators that lead to activation of EMT programs during these disease processes is providing new insights into the plasticity of cellular phenotypes and possible therapeutic interventions.

Bortezomib-melphalan-prednisone combination is one of the standards of care for nontransplant eligible patients with newly diagnosed multiple myeloma. However, bortezomib intravenous (twice weekly for 4 cycles then weekly for 5 cycles) results in ~13% of patients with grade 3-4 peripheral neuropathy. Bortezomib subcutaneous (SQ) and weekly delivery, improves tolerability without impairment of efficacy. The aim of this study was to evaluate the safety and effectiveness of SQ bortezomib-based combinations in nontransplant eligible patients with newly diagnosed myeloma in a real-world setting. A total of 135 patients (median age [range] = 76 [58-89], International Staging System-III = 54%, median follow-up = 14.8 months [1-40], Intensive group [twice weekly bortezomib] = 65%, Optimized group [weekly bortezomib] = 35%) were included and evaluable for safety, whereas 121 were evaluable for effectiveness. Overall response rate (95% CI) was 61% (53%, 71%) (complete response = 27%, very good partial response = 13%, and partial response = 21%) and median progression-free survival was 22.2 months (95% CI: 16.1-not reached). The 3-year overall survival was 75%. The most frequent grade 3-4 adverse events were thrombocytopenia (18%), neutropenia (17%), and anemia (11%). Peripheral neuropathy of any grade was observed in 44% of patients (2% with grade 3). Comparison between regimens (Intensive vs Optimized) showed similar overall response rate (57% vs 70%) and PFS (25 vs 19 months). A similar safety profile was observed between regimens. Thus, SQ bortezomib showed similar effectiveness and better tolerability as compared with results from intravenous bortezomib studies, and showing no differences either in effectiveness or safety in different bortezomib-based combinations.

Background The safety and efficacy of cardiac stem/progenitor cells (CSC) have been demonstrated in previous preclinical and clinical assays for heart failure. However, their optimal delivery route to the ischemic heart has not yet been assessed. This study was designed to determine by a non-invasive imaging technique (PET/CT) the biodistribution and acute retention of allogeneic pig CSC implanted by two different delivery routes, intracoronary (IC) and intramyocardial (IM), in a swine preclinical model of chronic ischemia–reperfusion. Methods Ischemia–reperfusion was induced in six Goettingen hybrid minipigs by 90 min coronary artery occlusion followed by reperfusion. Thirty days later, animals were allocated to receive IC (n = 3) or NOGA®-guided IM injection (n = 3) of 50 million of 18F-FDG/GFP-labeled allogeneic pig CSC. Acute retention was quantified by PET/CT 4 h after injection and cell engraftment assessed by immunohistochemical quantification of GFP+ cells three days post-injection. Results Biodistribution of 18F-FDG-labeled CSC was clearly visualized by PET/CT imaging and quantified. No statistical differences in acute cell retention (percentage of injected dose, %ID) were found in the heart when cells were administered by NOGA®-guided IM (13.4 ± 3.4%ID) or IC injections (17.4 ± 4.1%ID). Interestingly, engrafted CSC were histologically detected only after IM injection. Conclusion PET/CT imaging of 18F-FDG-labeled CSC allows quantifying biodistribution and acute retention of implanted cells in a clinically relevant pig model of chronic myocardial infarction. Similar levels of acute retention are achieved when cells are IM or IC administered. However, acute cell retention does not correlate with cell engraftment, which is improved by IM injection. Electronic supplementary material The online version of this article (doi:10.1186/s12967-017-1157-0) contains supplementary material, which is available to authorized users.

Background Cisplatin is a potent antitumor agent. However, toxicity and primary and secondary resistance are major limitations of cisplatin-based chemotherapy, leading to therapeutic failure. We have previously reported that mono-sulfonamide platinum complexes have good antitumor activity against different tumoral cell lines and with a different and better cytotoxic profile than cisplatin. Besides, N-sulfonamides have been used extensively in medicinal chemistry as bactericides, anticonvulsant, inhibitors of the carbonic anhydrase, inhibitors of histone deacetylases, and inhibitors of microtubule polymerization, among others. Methods We aimed to compare the cytotoxic effects of cisplatin and a trans-sulfonamide-platinum-complex (TSPC), in two human melanoma cell lines that differ in their TP53 status: SK-MEL-5, TP53 wild type, and SK-MEL-28, TP53 mutated. We performed cytotoxicity assays with both drugs, alone and in combination, cell cycle analyses, western blotting and immunoprecipitation, and fluorescence immunocytochemistry. Results TSPC had similar antiproliferative activity than cisplatin against SK-MEL-5 (3.24 ± 1.08 vs 2.89 ± 1.12 μM) and higher against SK-MEL-28 cells (5.83 ± 1.06 vs 10.17 ± 1.29 μM). Combination of both drugs inhibited proliferation in both cell lines, being especially important in SK-MEL-28, and showing a synergistic effect. In contrast to cisplatin, TSPC caused G1 instead G2/M arrest in both cell lines. Our present findings indicate that the G1 arrest is associated with the induction of CDKN1A and CDKN1B proteins, and that this response is also present in melanoma cells containing TP53 mutated. Also, strong accumulation of CDKN1A and CDKN1B in cells nuclei was seen upon TSPC treatment in both cell lines. Conclusions Overall, these findings provide a new promising TSPC compound with in vitro antitumor activity against melanoma cell lines, and with a different mechanism of action from that of cisplatin. Besides, TSPC synergism with cisplatin facilitates its potential use for co-treatment to reduce toxicity and resistance against cisplatin. TSPC remains a promising lead compound for the generation of novel antineoplastic agent and to explore its synergism with other DNA damaging agents.

Summary Background & aims Mortality resulting from influenza (flu) virus infections occurs primarily in the elderly through declining immunity. Studies in mice have suggested beneficial effects of selenium (Se) supplementation on immunity to flu but similar evidence is lacking in humans. A dietary intervention study was therefore designed to test the effects of Se-supplementation on a variety of parameters of anti-flu immunity in healthy subjects aged 50–64 years. Methods A 12-week randomized, double-blinded, placebo-controlled clinical trial (ClinicalTrials.govNCT00279812) was undertaken in six groups of individuals with plasma Se levels

Objective To design a novel ex vivo acquisition technique to establish a common framework to validate different segmentation techniques for oncological PET images. To evaluate several automatic segmentation algorithms on this set of images. Material and methods In 15 patients with cancer, ex vivo PET studies of surgical specimens removed during surgery were performed after injection of 18 F-FDG. Images were acquired in two scanners: a clinical PET/CT and a high-resolution PET scanner. Real tumor volume was determined in each patient, and a reference image was generated for segmentation of each tumor. Images were segmented with 12 automatic algorithms and with a standard method for PET (relative threshold at 42%) and results were evaluated by quantitative parameters. Results It has been possible to demonstrate by segmentation of PET images of surgical specimens that on high resolution PET images, 8 out of 12 evaluated segmentation techniques outperformed the standard method, whose value is 42%. However, none of the algorithms outperformed the standard method when applied on images from the clinical PET/CT. Due to the great interest of this set of PET images, all studies have been published on the Internet in order to provide a common framework for validation and comparison of different segmentation techniques. Conclusions We have proposed a novel technique to validate segmentation techniques for oncological PET images, acquiring ex vivo PET studies of surgical specimens. We have demonstrated the usefulness of this set of PET images by evaluating several automatic segmentation algorithms.

Purpose To evaluate the safety of peptide receptors radionuclide therapy (PRRT) of neuroendocrine tumors after 7.4 GBq 177Lu-DOTA-TATE by measurement of the radiation exposure rates. Methods For each patient the radiation levels (H∗(10)) were measured at 1 meter distance from the patient abdomen. Measurements were performed with a survey meter at different time points, over 4 days from the treatment administration of a prescribed activity of 7.4 GBq of 177Lu-DOTA-TATE. The first measure was accomplished at the end of the 177Lu-octreotate infusion and before voiding of bladder, while the others were done after emptied the bladder. Results 13 patients (36 cycles) were treated with a mean (standard deviation) activity of 6834 (688) MBq per cycle. Mean (maximum) dose rates measured at 1, 8, 24, 48 and 97 h (mean time) after treatment initiation were 32 (42), 15 (27), 9 (19) 7 (18) and 5 (11) μ Sv/h, respectively. At 8, 24, 48 and 97 h, 90% of the patients radiation levels were below 20, 16, 12 and 8.4 μ Sv/h, respectively. In relation to the first measurement, the mean uptakes were 47, 31, 24 and 16%. Considering the physical decay of the isotope, the dose limits for individual members of the public and an 8 h a day permanence at 1 m of the patient, the maximum dose rate allowed for patient release would be 13 μ Sv/h. Conclusions Taking into account the dose rates at 1 meter and the analysis of the specific conditions of the family and social environment of each patient, after 24 h of the treatment administration the patient can be released in 75% of cases.

Cancer cachexia is a frequent pathophysiological state associated to terminal stage cancer patients, characterized by a significant reduction in body weight and resistant to nutritional interventions. It is an unmet medical need, and its underlying mechanisms are not completely understood. Objectives: To measure multiple soluble cytokines in patients with cachexia, to develop new hypotheses on pathways and/or eventual therapeutic targets. Methods: This is part of a pilot, observational, cross-sectional, case-control, IRB-reviewed translational research in cancer patients with/without cachexia. Anthropometric, clinical and biochemical data from consenting eligible cancer patients were collected. Blood samples were collected from all the participants, and plasma was separated and immediately stored at -20°C until analysis. For this substudy, human 63-plex kits were purchased from eBiosciences and used according to the manufacturer's recommendations. Plates were read using a Luminex 200 instrument, and the assay was performed in the Human Immune Monitoring Center at Stanford University (CA, USA). Data were analyzed by univariate and multivariate methods, using error adjustments for multiple testings (False Discovery Rate, FDR). A total of 15 subjects were included in this study, 8 cachectic and 7 non-cachectic patients. Median age in cachectic group was 61.5 (36-81) years versus 63.9 (48-80) in non-cachectic group. The respective relative weight loss within the prior 3 months was 17.6% and 1.0%. Clinical, analytical and metabolomics from these patients have been reported elsewhere (doi: 10.1002/jcsm.12270). Of the 63 cytokines tested in our panel, 18 have been selected for fold-change (FC) analysis: for 12, their log2(FC)>1 (IL1RA, ENA78, IL8, GROA, IL23, MCP1, BDNF, PDGFB, IL18, IL21, RESISTIN, IL6), being the FC > 10x for IL1RA, ENA78, IL8, GROA and IL23. For the remaining 6, their log2(FC) < -1 (LEPTIN, GMCSF, IL12P40, IL1B, CD40L, IL5). The cytokines selected for their FDR were: LEPTIN, LIF, GMCSF, RESISTIN, TNFA, IL1B, IL12P40, IL4, IL12p70, BDNF, IL2, IL5, IL23, IL17A and IL13. We integrated these results with prior metabolomics research and performed pathway analyses that enabled us to identify a significant enrichment in several pathways related with infections, immune response, inflammation, energy homeostasis and cancer. This study, despite the size constraints, is able to capture known players in cancer cachexia (leptin, IL6, IL1). We show a potential role for BDNF (brain derived neurotrophic factor), which and has been described as a master coordinator of the physiological mechanisms that regulate food intake and energy expenditure, and identified as a player in murine models for cancer cachexia. Results from this study will be integrated with data from additional research in the same patients (clinical, analytical, metabolomics and proteomics). Citation Format: Mª Teresa Agullo-Ortuño, Virginia Pardo-Marques, Elena Prieto-Garcia, C. Vanesa Diaz-Garcia, Irene Otero, Jose A. Lopez-Martin. A translational multiplexed hypothesis generating study on circulating cytokines in patients with cancer cachexia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4854.

Resumen Objetivo Caracterizar el funcionamiento del tomografo PET/TAC Biograph mCT TrueV que incorpora el tiempo de vuelo (TOF) y modeliza la respuesta a una fuente puntual (PSF). Material y metodos El tomografo combina un TAC de 64 cortes y un PET que reconstruye tomograficamente con TOF y PSF. Las caracteristicas de funcionamiento PET se evaluaron siguiendo el estandar NEMA NU-2-2007, ampliando algunas pruebas. Adicionalmente se evaluaron diferentes algoritmos de reconstruccion y se midieron la radiacion intrinseca y la uniformidad tomografica. Resultados La resolucion espacial (FWHM) a 1 y 10 cm del eje fue de 4,4 y 5,3 mm, mejorando al introducir la PSF a 2,6 y 2,5 mm. La sensibilidad fue de 10,9 y 10,2 kcps/MBq a 0 y 10 cm del eje. La fraccion de dispersion fue inferior al 34% a bajas concentraciones y la tasa de sucesos equivalentes al ruido (NECR) fue maxima en 182 kcps a 27,8 kBq/mL. La radiacion intrinseca produjo 4,42 coincidencias verdaderas por segundo. El coeficiente de variacion de la uniformidad del volumen y del sistema fue del 4,7 y 0,8%. La prueba de calidad de imagen mostro mejores resultados al incluir conjuntamente PSF y TOF. Especificamente, la PSF mejoro el contraste de las esferas calientes y la variabilidad del fondo, mientras que el TOF aumento el contraste de las esferas frias. Conclusiones El tomografo tiene muy buenas caracteristicas de funcionamiento, ademas la calidad de la imagen mejora al incorporar la informacion de la PSF y del TOF en la reconstruccion tomografica.

Porphobilinogen deaminase (PBGD) haploinsufficiency (acute intermittent porphyria, AIP) is characterized by neurovisceral attacks when hepatic heme synthesis is activated by endogenous or environmental factors including fasting. While the molecular mechanisms underlying the nutritional regulation of hepatic heme synthesis have been described, glucose homeostasis during fasting is poorly understood in porphyria. Our study aimed to analyse glucose homeostasis and hepatic carbohydrate metabolism during fasting in PBGD-deficient mice. To determine the contribution of hepatic PBGD deficiency to carbohydrate metabolism, AIP mice injected with a PBGD-liver gene delivery vector were included. After a 14 h fasting period, serum and liver metabolomics analyses showed that wild-type mice stimulated hepatic glycogen degradation to maintain glucose homeostasis while AIP livers activated gluconeogenesis and ketogenesis due to their inability to use stored glycogen. The serum of fasted AIP mice showed increased concentrations of insulin and reduced glucagon levels. Specific over-expression of the PBGD protein in the liver tended to normalize circulating insulin and glucagon levels, stimulated hepatic glycogen catabolism and blocked ketone body production. Reduced glucose uptake was observed in the primary somatosensorial brain cortex of fasted AIP mice, which could be reversed by PBGD-liver gene delivery. In conclusion, AIP mice showed a different response to fasting as measured by altered carbohydrate metabolism in the liver and modified glucose consumption in the brain cortex. Glucose homeostasis in fasted AIP mice was efficiently normalized after restoration of PBGD gene expression in the liver.

Bendamustine is a alkylating agent with a purine-like benzamidazole ring currently approved in Europe for indolent non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma. Our aim was to analyze retrospectively the efficacy and toxicity of bendamustine in NHL and CLL in Spain in the bendamustine Compassionate Use Program. Patients with relapsed/refractory NHL or CLL were eligible. Any regimen containing bendamustine was eligible. 109 patients were included from 22 institutions. Forty-nine patients had indolent NHL, 18 aggressive NHL and 42 CLL, being 44 patients (40%) refractory to previous treatment. 63% of patients had adverse events grade 3-4, mainly hematological. Overall response rate (ORR) was 66%, complete responses 30%. ORR observed in refractory patients was 45%. The median progression-free survival (PFS) was 13 months. Outcome was influenced by histology, number of previous treatments, resistance to previous chemotherapy and type of response achieved with bendamustine. Alone or in combination, bendamustine shows a meaningful clinical antitumor activity in patients with relapsed or refractory NHL or CLL, with an acceptable toxicity profile.

The aim of the study was to evaluate the volumetric integration patterns of standard MRI and 11C-methionine positron emission tomography (PET) images in the surgery planning of gliomas and their relationship to the histological grade. We studied 23 patients with suspected or previously treated glioma who underwent preoperative 11C-methionine PET because MRI was imprecise in defining the surgical target contour. Images were transferred to the treatment planning system, coregistered and fused (BrainLAB). Tumour delineation was performed by 11C-methionine PET thresholding (vPET) and manual segmentation over MRI (vMRI). A 3-D volumetric study was conducted to evaluate the contribution of each modality to tumour target volume. All cases were surgically treated and histological classification was performed according to WHO grades. Additionally, several biopsy samples were taken according to the results derived either from PET or from MRI and analysed separately. Fifteen patients had high-grade tumours [ten glioblastoma multiforme (GBM) and five anaplastic), whereas eight patients had low-grade tumours. Biopsies from areas with high 11C-methionine uptake without correspondence in MRI showed tumour proliferation, including infiltrative zones, distinguishing them from dysplasia and radionecrosis. Two main PET/MRI integration patterns emerged after analysis of volumetric data: pattern vMRI-in-vPET (11/23) and pattern vPET-in-vMRI (9/23). Besides, a possible third pattern with differences in both directions (vMRI-diff-vPET) could also be observed (3/23). There was a statistically significant association between the tumour classification and integration patterns described above (p

Purpose Although specific positron emission tomography (PET) scanners have been developed for small animals, spatial resolution remains one of the most critical technical limitations, particularly in the evaluation of the rodent brain. The purpose of the present study was to examine the reliability of voxel-based statistical analysis (Statistical Parametric Mapping, SPM) applied to 18F-fluorodeoxyglucose (FDG) PET images of the rat brain, acquired on a small animal PET not specifically designed for rodents. The gold standard for the validation of the PET results was the autoradiography of the same animals acquired under the same physiological conditions, reconstructed as a 3-D volume and analysed using SPM.

Resumen La 18 F-FDOPA es un analogo de aminoacidos empleado en la evaluacion de la funcion dopaminergica presinaptica, que ha despertado gran interes en neuro-oncologia. Evaluamos 5 estudios PET con 18 F-FDOPA de pacientes remitidos para estudio por sindrome parkinsoniano. Dos de ellos tuvieron tumores cerebrales de alto grado previamente tratados, uno una lesion cerebral inespecifica y dos tenian un hallazgo incidental de tumor cerebral. Para cada lesion se calculo el SUVmax, el tiempo a SUVmax y el indice SUVmax entre la lesion y la sustancia gris (T/N), y se analizo el perfil de la cinetica de captacion. Las lesiones tumorales correspondieron a tres neurocitomas malignos, un meningioma, un pineocitoma y un hemangioma intrasinusal. Todas las lesiones tumorales mostraron una captacion de 18 F-FDOPA superior al cortex sano. El analisis de la curva cinetica de la 18 F-FDOPA mostro una doble fase de maxima captacion que facilito la caracterizacion tumoral: una fase inicial a los 10 minutos en lesiones malignas, y una fase tardia a los 60-90 minutos en las benignas o de bajo grado.

(18)F-FDOPA is an amino acid analogue used to evaluate presynaptic dopaminergic activity, which has aroused great interest in neuro-oncology. We have evaluated five (18)F-FDOPA PET studies of patients referred for study of parkinsonian syndrome. Two subjects had previously treated high-grade brain tumors, one nonspecific brain injury, and 2 subjects presented unexpected tumoral lesions. For all lesions SUVmax, time to SUVmax and tumor-to-normal grey matter SUVmax rate (T/N) were calculated, and 90 minutes (18)F-FDOPA kinetics were analyzed. Tumor lesions corresponded to three malignant neurocytomas, one meningioma, one pineocytoma and one intrasinusal hemangioma. Both malignant and benign tumors exhibited high uptake of (18)F-FDOPA well above the normal cortex. However, the analysis of the curve uptake displayed characteristic patterns that facilitate the characterization of tumor lesions. A dual phase maximum uptake was observed, with an early 10 minutes uptake in malignant lesions, and a late 60 to 90 minutes uptake in benign or low grade lesions.

Introduction The comprehensive geriatric assessment (CGA) in older patients with cancer is the gold standard to identify robust, frail or poor prognosis patients according Balducci classification. In Spain, a new proposal of a specific Geriatric Assessment in Hematology (GAH) scale has been designed and validated in patients with hematologic malignancies such as MDS/AML, multiple myeloma and CLL. The GAH scale has not been explored in patients with lymphoma. In this study, we have analyzed the utility of using the GAH scales in patients with hematologic malignancies, mostly lymphoma patients. Patients and methods. From March 2016 and September 2017, patients with hematologic malignancies were prospectively referred to the Geriatric Oncology clinic after a frailty screening test using G8 scale and with score Results Of the 96 patients referred aged 70 years or over, 41 were males (42.7%) and 55 females (57.3%), the median age was 79 years (range, 70-89), and with the diagnosis of lymphoma in 53 patients (55.2%), multiple myeloma in 23 patients (24.0%), CLL in 13 patients (13.6%), MDS/AML in 5 patients (5.2%) and CML in 2 patients (2.0%). Seventy-five patients (78.1%) had good performance status with ECOG score 0-1. Regarding frailty, 20 patients (20.8%) had a score of 15 points or over at G8 scale and 76 patients (79.2%) were identified as frail because of a score of 14 points or below. Regarding comorbidities, the median CIRS-G score was 9 (range, 4-20). After the GAH scale assessment, the median number of domains affected in robust patients was 2 (1-4) and in frail patients was 4 (3-5) (p=0.0001). In the ROC curve, with an AUC of 0.7595 and a likelyhood ratio of 9, the cut-off in this series was 2 domains with impairment, with a sentivity of 13.79% and a specificity of 92.5% (p= 0.0003). Using a correlation factor for each domain, the mean score at GAH scale in robust patients was 26 points and in frail patients was 42.5 points (p=0.0038). In the ROC curve, with an area under the curve of 0.7026 and a likelihood ratio of 2.04, the cut-off value to identify robust vs frail patients was 33 points in the GAH scale, with a sensitivity of 77.5% and a specificity of 62.07% (p=0.0043). Analyzing the eight domains explored in the GAH scale, robust patients according CGA had less risk of polypharmacy of 31.25% vs 81.48% in frail patients (OR 0.1033, 95% CI 0.0472-0.2541) (p Mean G8 score were similar between robust (11.68) and frail (11.04) patients (p=n.s.) among all patients with score below 14 points. Robust patients had less comorbidities according to CIRS-G scale, with a median of 9 vs 11 points (p=0.0001). There was correlation between CIRS-G and ECOG with G8 score, not found in previous studies. There is a correlation between the brief comorbidity assessment in the GAH scale with CIRS-G score. Among patients identified as not having comorbidities, the median CIRS-G score was 9 vs 13.5 among patients with comorbidities according the GAH scale (p Conclusions. The GAH scale is a valid tool for patients with hematologic malignancies, including patients with lymphoma, in order to classify patients according frailty phenotype. All domains explored in GAH scale were impaired with higher frequency in frail patients. Robust patients had less comorbidities and better performance status. The brief comorbidities assessment in the GAH scale correlates well with the CIRS-G. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Neuroimaging using both functional and structural examinations like positron emission tomography (PET), single photon emission tomography (SPECT), computed tomography (CT) and magnetic nuclear imaging (MRI) provide supportive information of great importance for the diagnosis and treatment of patients with central nervous system disorders. Therefore, they have become commonplace in clinical practice and basic biomedical research. In recent years we have seen the development of multimodality equipment that enables PET or SPECT to be combined with a CT structural image. Moreover, experimental equipment combining PET and MRI has now been developed. Additionally, methodological features that provide a higher image quality, and analysis tools for objective quantification and interpretation have been refined. This article reviews the technical aspects of those imaging methods, highlighting the most significant and recent advances in the development of neuroimaging.

The employment of current treatments based on chemotherapy and immunotherapy leads to inmunosuppression. The presence of mutations or polymorphisms in genes related to immune system might involve an additional disadvantage. The aim of the present study was to analyze mannose-binding lectin (MBL-2 gene) mutations and their association with severe infections and event-free survival in patients diagnosed with follicular lymphoma, treated uniformly, in the clinical trial LNHF-03. The results of this trial showed impressive clinical efficacy but was complicated with 80 documented infectious episodes. Patients were classified into two genotypic groups, AA and AO/OO, based on their haplotypic inheritance. Neither the number of infectious episodes nor differences in event-free survival was found as a function of MBL-2 groups. Other factors, including the lymphoma malignancy and the immune alterations associated with the disease, should be considered responsible for this observation.

The study of regional cerebral metabolism by positron emission tomography (PET) can be applied to the primary and associative auditory cortices, providing important information about normal hearing, hearing loss, and the neuroplasticity processes of the auditory system. We have reviewed the pertinent literature to provide the most significant facts that may help clinicians in the selection phase of a cochlear implant programme. PET-scan studies offer vital information concerning the time process for hearing restoration in cases of severe-profound hearing impairment. Additionally, we report a short case series of eight patients with long-lasting unilateral profound hearing loss combined with the contralateral ear having some functional hearing. These patients are quite difficult to counsel in the process of selection for cochlear implantation, as there is a lack of functional information on neural plasticity. PET-scan studies permit an evaluation of activation of both primary auditory cortices in patients ...

Resumen La dihidrotetrabenazina (2-hidroxi-3-isobutil- 9,10-dimetoxi-1,3,4,6,7-hexahidro-11bH-benzo[a]-quinolizina, DTBZ) se ha convertido en el ligando ideal de los transportadores presinapticos de monoaminas (VMAT2) debido a su elevada afinidad de union y su lipofilicidad. Objetivo Desarrollar un procedimiento de sintesis automatico para el marcaje con carbono-11 de la DTBZ para utilizarla como marcador en el estudio in vivo mediante tomografia por emision de positrones de perdidas neuronales en modelos animals de enfermedad de Parkinson. Material y metodos Se ha disenado un nuevo metodo de sintesis totalmente automatizado para la obtencion de 11C-(+)DTBZ. La reaccion de metilacion del precursor -(+)desmetildihidrotetrabenazina– se lleva a cabo a temperatura ambiente, a partir de la obtencion de 11CH3I que utilizamos como precursor primario, en presencia de dimetilsulfoxido e hidroxido de potasio. Para los procesos de purificacion se han utilizado cartuchos de extraccion en fase solida alumina y los disolventes residuales del producto final se eliminaron mediante evaporacion bajo flujo de helio. Resultados De las 54 sintesis realizadas se han obtenido, con un tiempo de bombardeo de 5 minutos, y 6 minutos de sintesis tras la obtencion de 11CH3I, unas producciones medias de 1,94 ± 0,13 GBq de 11C-(+)DTBZ, esteril, apirogeno y con una pureza radioquimica > 99%. Conclusiones Este nuevo procedimiento de sintesis es rapido y simple, ya que para la purificacion final se han optimizado tecnicas que permitieran la eliminacion de los disolventes residuales basandonos en su polaridad y es aplicable a otras sintesis automaticas para la obtencion de otros compuestos marcados mediante reacciones de metilacion.

Dihydrotetrabenazine (2-hydroxy-3-isobutyl-9,10-dimethoxy-1,3,4,6,7-hexahydro-11bH-benzo[a]-quinolizine, DTBZ) has become the ideal radioligand for the presynaptic vesicular monoamine transporter VMAT2 based on its high binding affinity and optimal lipophilicity. Objective To develop an automatic procedure for labelling DTBZ with carbon-11, which has been shown to be a highly effective marker for in vivostudies of neuronal losses in animal models with Parkinson's disease using positron emission tomography (PET). Materials and methods We have developed a new fully automated synthesis procedure to obtain 11 C-(+)DTBZ quickly and simply through labelling the precursor –(+)desmethyldihydrotetrabenazine– at room temperature in the presence of dimethyl sulfoxide (DMSO) and potassium hydroxide (KOH), using 11 CH 3 I as primary precursor. The final purification was carried out by solid phase extraction using commercially available cartridges and the residual solvents (DMSO and ethyl ether) were eliminated by evaporation. Results The whole procedure was automated, and after 54 syntheses, an average production of 1.94 GBq of sterile, pyrogen- free 11 C-(+)DTBZ with a radiochemical purity > 99% was obtained with 5 minutes irradiation and 6 minutes of synthesis after 11 CH 3 I production. 11 C-(+)DTBZ binding to presynaptic dopamine nerve terminals has been demonstrated by MicroPET studies in Wistar rats and M. Fascicularismonkeys. Conclusions This new synthesis procedure is quick and simple, due to optimised techniques, which have allowed elimination of residual solvents based on their polarity for the final purification. It is also applicable to other automatic syntheses for obtaining compounds labelled by methylation reactions.