Notes

Maps Sphingolipid Metabolism Pathways in the course of Phagosomal Growth.
Psoriatic skin lesions are metabolically active, which makes them candidates for imaging with 18-F fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). The aim of our study was to correlate FDG-PET findings with Psoriasis Area and Severity Index (PASI) scores, the most widely-used grading system for psoriasis. Thirty-three subjects and a total of 84 FDG-PET/CT scans from a prospective clinical trial [NCT01553058] with >2 months moderate-to-severe psoriasis were included. Subjects underwent whole-body FDG-PET/CT imaging 60 min after intravenous FDG administration, prior to the start of treatment. Scans were repeated 12 weeks and 52 weeks after baseline scans were conducted and after treatment or placebo administration was initiated. Each subject and scan was graded by our "PET-PASI" scoring system, a qualitative review of multi-plane reconstructions for both attenuation-corrected (AC) and non-attenuation-corrected (NAC) PET images. PASI and PET-PASI scores were correlated using Spearman's rho analysis. Our study demonstrated a significant positive correlation between each subject's corresponding PET-PASI and PASI scores before and during treatment or placebo administration (r=0.53, P less then 0.001). We also found positive correlations between PET-PASI and PASI scores across different regions of the body (head and neck r=0.22, upper extremities r=0.26, trunk r=0.48, and lower extremities r=0.58). In conclusion, AC and NAC FDG-PET/CT images may be utilized to evaluate lesions in subjects with moderate-to-severe psoriasis. Our methodology could have future implications in the diagnosis and therapeutic management of psoriasis.The practical application of dual-time-point-imaging (DTPI) technique still remains controversial. One of the issues is that current parameters of DTPI quantification suffer from some deficiencies, mainly limited sampling of the diseased sites by confining measurements to specific locations. We aimed to examine the correlation between the percent change from early to delayed scans in whole-bone marrow (WBM) 18F-FDG uptake, as measured by a CT-based method of PET/CT quantification, and response to treatment in multiple myeloma (MM) patients. Pre-treatment 18F-FDG-PET/CT scans of 36 newly diagnosed MM patients were collected in a prospective study at 1 h and 3 h post tracer injection (NCT02187731). A threshold algorithm based on bone Hounsfield units on CT was applied to segment and quantify WBM 18F-FDG uptake. Patients were separated into two treatment groups high-dose therapy with autologous stem cell transplant (HDT) and non-high dose therapy (non-HDT). The International Response Criteria for MM patients was used to determine each patient's response to treatment. In the HDT group, WBM 18F-FDG uptake increased significantly in patients that had a poor response to treatment, from a median of 1.31 (IQR 1.13-1.64) at 1 h to a median of 1.85 (1.45-2.10) at 3 h. The median percent change was 37.77% (IQR 23.47-46.4), with a range of 6.10-50.73 (P = 0.003). However, no significant change in uptake was observed in patients with a complete response (P = 0.24). The same trend was observed for the non-HDT group. WBM uptake of 18F-FDG assessed with dual-time-point imaging may have a role in predicting treatment response in MM.MAG3 scintigraphy with determination of split renal function (SRF) is a standard procedure in patients with metastasized castration-resistant prostate carcinoma (mCRPC) undergoing PSMA radioligand therapy (PSMA-RLT). These patients also receive frequent PSMA PET/CT scans for staging and follow up. PSMA is not only overexpressed in prostate cancer epithelial cells, but also physiologically overexpressed in the proximal tubular cells of the kidney. This study investigates the utility of PSMA-targeted imaging for determination of relative renal function. mCRPC patients (n = 97) having received 68Ga-PSMA-11 PET/CT and 99mTc-MAG3 scintigraphy in close temporal relationship were included in this retrospective study. PSMA-PET-derived SRF was calculated according to the bilateral renal PSMA content (total kidney PSMA = SUVmean × volume), MAG3-based SRF (SRFMAG3) using the common standard integral method of the renal secretion phase. The agreement of SRFPSMA and SRFMAG3 was statistically tested using Pearson correlation and Bland-Altman analysis. The correlation between both SRF assessment methods was highly significant (P less then 0.001) with r=0.91. Bland-Altman analysis confirmed agreement of the measurements. selleck and agreement were also observed in the subgroup analyses of patients with normal and reduced renal function (r=0.81, P less then 0.001 and r=0.98, P less then 0.001). Renal tubular PSMA expression allows assessment of split renal function by 68Ga-PSMA-11 PET/CT imaging. Additional MAG3 scintigraphy for the purpose of quantifying relative renal function contribution may be spared in settings where PSMA PET is performed; this insight could save time and unnecessary examinations.We determined the optimal imaging time for axillary lymph node (LN) visualization following Tc-99m Tilmanocept in breast cancer patients to establish imaging guidelines that can allow for a reliable and efficient yet high yield study prior to surgery. Retrospective analysis in 651 patients who underwent lymphoscintigraphy, comparing LN visualization on immediate, 15-minute, and 90-minute delayed imaging after injection of Tc-99m Tilmanocept. Statistical analysis was performed using McNemar's test, kappa coefficient, and Pearson Chi-square test. Five hundred and six patients had either immediate or immediate and 90-minute delayed imaging. Of these patients, 203 (40.1%) had both immediate and 90-minute delayed images. Of these 203 patients, 54 (26.6%) had ≥1 lymph node(s) identified immediately and 196 (96.6%) had ≥1 lymph node(s) identified at 90 minutes (P less then 0.0001). A kappa coefficient of .0256 was observed (95% CI .0058-.0453). #link# One hundred and forty-five additional patients had 15-minute delayed imaging. Of these patients, 117 (80.7%) had ≥1 lymph node(s) identified, which was significantly fewer compared to the number of patients with ≥1 lymph node(s) detected at 90 minutes (P less then 0.0001). Ninety-minute delayed imaging is optimal for identifying sentinel lymph node(s) following Tc-99m Tilmanocept injection in breast cancer patients.To evaluate the effectiveness of radioactive iodine (131I) therapy in patients with Graves' disease (GD) in Assiut University Hospital. We retrospectively evaluated two hundred and seven patients with GD, after their therapy with 131I. Before therapy all the included patients underwent neck ultrasound, hormonal assay and 99mTechnetium-pertechntate (99mTc) thyroid scintigraphy to evaluate percentage uptake of the thyroid gland, after therapy all patients followed up clinically and laboratory every 3 months for at least one year to detect outcome; where euthyroid or hypothyroid status denotes successful therapy. Successful outcome obtained in 165/207 patients representing 79.7% of the study population while in the remaining 42 (20.3%) patients a second dose was required. In Univariate analysis only dose of 131I and previous thyroid surgery are the important factors (P value = 0.003 and 0.001 respectively). We concluded that 131I therapy is highly effective and cost-effective method for treatment of GD, higher doses are associated with higher success rate.[11C]5-Hydroxy-tryptophan ([11C]5-HTP) is a Positron Emission Tomography marker for serotonergic biosynthesis and degradation, with use in imaging of neuroendocrine tumors and recently also the endocrine pancreas in diabetes. In order to further develop [11C]5-HTP as a quantitative in vivo tool for understanding the mechanisms of serotonin signaling in human pancreas, we aimed to develop a kinetic modeling approach sensitive for changes in serotonin biosynthesis, retention and degradation. Cynomolgus monkeys were examined by [11C]5-HTP PET/CT, either at baseline (n=9) or following intravenous pretreatment with 3 mg/kg carbidopa (Dopa Decarboxylase inhibitor, n=3) or 2 mg/kg clorgyline (Monoamine Oxidase-A inhibitor, n=5). The dynamic tissue uptake was analysed by a 2-tissue compartment model including an efflux mechanism from the second tissue compartment (2TC kloss), which theoretically reproduces the known processing of 5-HTP in neuroendocrine cells. The 2TC kloss model could accurately describe all three modes of tissue kinetics depending on the pretreatment regiment. Rate constant k3 (corresponding to DDC activity) and the macro-parameter Flux (Ki) was decreased (P less then 0.05) by carbidopa pretreatment, while k2 (corresponding to cellular washout of intact [11C]5-HTP) was increased (P less then 0.05). The efflux parameter kloss (corresponding to MAO-A activity) was decreased (P less then 0.05) by pretreatment of clorgyline, while the macro-parameter Flux/Efflux ratio (Ki/kloss) was increased (P less then 0.0001). We present a compartment model analysis method that can quantitatively assess in vivo pharmacological interactions with several of the key enzymatic steps of the serotonergic biosynthesis in pancreas.High liver uptake presents a problem for 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) as a radiotracer for imaging cellular proliferation in the liver with positron emission tomography (PET). This investigation re-visited some issues related to the high liver background uptake of [18F]FLT with an animal model of woodchucks. Several enzymes involved in the hepatic catabolism of FLT, thymidine phosphorylase (TP, TYMP), uridine 5'-diphospho-glucuronosyl-transferases (UDP-GTs, short for UGTs), and β-glucuronidase (GUSB), their homology as well as hepatic expression between the human and the woodchuck was examined. Inhibitors of these enzymes, TP inhibitor (TPI) tipiracil hydrochloride, UGT inhibitor probenecid, β-glucuronidase inhibitor L-aspartate, were administered to the animals at human equivalent doses either intravenously (i.v.) and orally before the injection of tracer-dose [18F]FLT for PET imaging to examine any changes in liver uptake. Liver tissue samples were harvested from the animals after PET imaging and used to perform polymerase chain reaction (PCR) for TP expression or assays for enzymatic activities of TP and β-glucuronidase. link2 Non-radiolabeled (cold) FLT was also applied for enzyme saturation. link3 Animals administered with TPI displayed lower radioactivity in the liver in comparison with the baseline scan. The application of probenecid did not change [18F]FLT liver uptake even though it reduced renal uptake. L-aspartate reduced the liver background uptake of [18F]FLT slightly. The application of cold FLT reduced overall uptake of [18F]FLT including the liver background. Therefore, the combined application of cold FLT and [18F]FLT merits further clinical investigation for reducing liver background uptake of [18F]FLT.Anxiety is common among patients with burn injury, occurring frequently surrounding wound care. Few pharmacologic interventions targeting anxiety in burn injury have been evaluated. This study aimed to evaluate patient-controlled anxiolysis using dexmedetomidine (PCA-DEX) in patients undergoing burn dressing changes. This was a prospective, open-label, single-arm pilot study to determine the feasibility, safety, and acceptability of PCA-DEX. PCA-DEX included a loading dose, continuous infusion, and patient-administered boluses during dressing changes for up to 5 days. Vital signs were monitored throughout PCA-DEX. Procedural pain and anxiety were evaluated before and after each dressing change. Nursing and patient satisfaction were evaluated after each dressing change. Twenty patients were included; 9 (45%) males and 11 females (55%) with a mean age of 45.1 ± 16.9 years and median total body surface area burn injury of 7 [IQR 4-9.5]%. Median heart rate and systolic blood pressure prior to PCA-DEX on day 1 were 82 [75-97] bpm and 147 [128-170] mmHg.
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