Automated radiosynthesis of Al[18F]PSMA-11 for large scale routine use.

Objectives: We report a reproducible automated radiosynthesis for large scale batch production of clinical grade Al[F-18]PSMA-11. Methods: A SynthraFCHOL module was optimized to synthesize Al[F-18]PSMA-11 by Al[F-18]-chelation. Results Al[F-18]PSMA-11 was synthesized within 35 min in a yield of 21 +/- 3% (24.0 +/- 6.0 GBq) and a radiochemical purity > 95%. Batches were stable for 4 h and conform the European Pharmacopeia guidelines. Conclusions: The automated synthesis of Al[F-18]PSMA-11 allows for large scale production and distribution of Al [F-18]PSMA-11

Zehra

Nabizade Nazım'ın Servet-i Fünun'da tefrika edilen Zehra adlı roman

Assessment of bone graft incorporation by 18 F-fluoride positron-emission tomography/computed tomography in patients with persisting symptoms after posterior lumbar interbody fusion

BACKGROUND: Posterior lumbar interbody fusion (PLIF) is a method that allows decompression of the spinal canal and nerve roots by laminectomy combined with fusion by means of intervertebral cages filled with bone graft and pedicle screw fixation. Conventional imaging techniques, such as plain radiography and computed tomography (CT), have limitations to assess bony fusion dynamics. METHODS: In 16 PLIFs of 15 patients with persisting symptoms, positron-emission tomography (PET)/CT scans were made 60 min after intravenous administration of 156 to 263 MBq of (18) F-fluoride, including 1-mm sliced, high-dose, non-contrast-enhanced CT scanning. Maximal standard uptake values (SUVmax) of various regions were calculated and correlated with abnormalities on CT. RESULTS: Subsidence of the cages into the vertebral endplates was the most frequently observed abnormality on CT (in 16 of 27 or 59% of evaluable endplates). Endplate SUVmax values were significantly higher for those patients with pronounced (p < 0.0001) or moderate (p < 0.013) subsidence as compared to those with no subsidence. Additionally, a significant correlation between vertebral and ipsilateral pedicle screw entrance SUVmax values (p < 0.009) was found, possibly indicating posterior transmission of increased bone stress. In our patient group, intercorporal fusion was seen on CT in 63% but showed no correlation to intercorporal SUVmax values. CONCLUSIONS: With the use of (18) F-fluoride PET/CT, intervertebral cage subsidence appeared to be a prominent finding in this patient group with persisting symptoms, and highly correlating with the degree of PET hyperactivity at the vertebral endplates and pedicle screw entry points. Further study using (18) F-fluoride PET/CT should specifically assess the role of metabolically active subsidence in a prospective patient group, to address its role in nonunion and as a cause of persisting pain

Quantitative imaging for targeted radionuclide therapy dosimetry : technical review

Targeted radionuclide therapy (TRT) is a promising technique for cancer therapy. However, in order to deliver the required dose to the tumor, minimize potential toxicity in normal organs, as well as monitor therapeutic effects, it is important to assess the individualized internal dosimetry based on patient-specific data. Advanced imaging techniques, especially radionuclide imaging, can be used to determine the spatial distribution of administered tracers for calculating the organ-absorbed dose. While planar scintigraphy is still the mainstream imaging method, SPECT, PET and bremsstrahlung imaging have promising properties to improve accuracy in quantification. This article reviews the basic principles of TRT and discusses the latest development in radionuclide imaging techniques for different theranostic agents, with emphasis on their potential to improve personalized TRT dosimetry

Brown Adipose Tissue in Morbidly Obese Subjects

BACKGROUND: Cold-stimulated adaptive thermogenesis in brown adipose tissue (BAT) to increase energy expenditure is suggested as a possible therapeutic target for the treatment of obesity. We have recently shown high prevalence of BAT in adult humans, which was inversely related to body mass index (BMI) and body fat percentage (BF%), suggesting that obesity is associated with lower BAT activity. Here, we examined BAT activity in morbidly obese subjects and its role in cold-induced thermogenesis (CIT) after applying a personalized cooling protocol. We hypothesize that morbidly obese subjects show reduced BAT activity upon cold exposure. METHODS AND FINDINGS: After applying a personalized cooling protocol for maximal non-shivering conditions, BAT activity was determined using positron-emission tomography and computed tomography (PET-CT). Cold-induced BAT activity was detected in three out of 15 morbidly obese subjects. Combined with results from lean to morbidly obese subjects (n = 39) from previous study, the collective data show a highly significant correlation between BAT activity and body composition (P<0.001), respectively explaining 64% and 60% of the variance in BMI (r = 0.8; P<0.001) and BF% (r = 0.75; P<0.001). Obese individuals demonstrate a blunted CIT combined with low BAT activity. Only in BAT-positive subjects (n = 26) mean energy expenditure was increased significantly upon cold exposure (51.5±6.7 J/s versus 44.0±5.1 J/s, P = 0.001), and the increase was significantly higher compared to BAT-negative subjects (+15.5±8.9% versus +3.6±8.9%, P = 0.001), indicating a role for BAT in CIT in humans. CONCLUSIONS: This study shows that in an extremely large range of body compositions, BAT activity is highly correlated with BMI and BF%. BAT-positive subjects showed higher CIT, indicating that BAT is also in humans involved in adaptive thermogenesis. Increasing BAT activity could be a therapeutic target in (morbid) obesity

Sentinel node in ovarian cancer : study protocol for a phase 1 study

Background: The concept of sentinel lymph node surgery is to determine whether the cancer has spread to the very first lymph node or sentinel node. If the sentinel node does not contain cancer, then there is a high likelihood that the cancer has not spread to other lymph nodes. The sentinel node technique has been proven to be effective in different types of cancer. In this study we want to determine whether a sentinel node procedure in patients with ovarian cancer is feasible when the tracers are injected into the ovarian ligaments. Methods/Design: Patients with a high likelihood of having an ovarian malignancy in whom a median laparotomy and a frozen section analysis is planned and patients with endometrial cancer in whom a staging laparotomy is planned will be included. Before starting the surgical staging procedure, blue dye and radioactive colloid will be injected into the ligamentum ovarii proprium and the ligamentum infundibulo-pelvicum. In the analysis we calculate the percentage of patients in whom it is feasible to identify sentinel nodes. Other study parameters are the anatomical localization of the sentinel node(s) and the incidence of false negative lymph nodes

Hypoxia imaging with 18F-FAZA PET/CT predicts radiotherapy response in esophageal adenocarcinoma xenografts

Background: Esophageal cancer is an aggressive disease with poor survival rates. A more patient-tailored approach based on predictive biomarkers could improve outcome. We aimed to predict radiotherapy (RT) response by imaging tumor hypoxia with F-18-FAZA PET/CT in an esophageal adenocarcinoma (EAC) mouse model. Additionally, we investigated the radiosensitizing effect of the hypoxia modifier nimorazole in vitro and in vivo. Methods: In vitro MTS cell proliferation assays (OACM5 1.C SC1, human EAC cell line) were performed under normoxic and hypoxic (< 1%) conditions: control (100 mu L PBS), nimorazole, irradiation (5, 10 or 20 Gy) with or without nimorazole. In vivo, subcutaneous xenografts were induced in nude mice (OACM5 1.C SC1). Treatment was given daily for 5 consecutive days: (A) control (600 mu l NaCl 0.9% intraperitoneally (IP)) (N = 5, n = 7), (B) RT (5 Gy/d) (N = 11, n = 20), (C) combination (nimorazole (200 mg/kg/d IP) 30 min before RT) (N = 13, n = 21). N = number of mice, n = number of tumors. F-18-FAZA PET/CT was performed before treatment and tumor to background (T/B) ratios were calculated. Relative tumor growth was calculated and tumor sections were examined histologically (hypoxia, proliferation). Results: A T/B= 3.59 on pre-treatment F-18-FAZA PET/CT was predictive for worse RT response (sensitivity 92.3%, specificity 71.4%). Radiation was less effective in hypoxic tumors (T/B = 3.59) compared to normoxic tumors (T/B < 3.59) (P = 0.0025). In vitro, pre-treatment with nimorazole significantly decreased hypoxic radioresistance (P < 0.01) while in vivo, nimorazole enhanced the efficacy of RT to suppress cancer cell proliferation in hypoxic tumor areas (Ki67, P = 0.064), but did not affect macroscopic tumor growth. Conclusions: Tumor tissue hypoxia as measured with F-18-FAZA PET/CT is predictive for RT response in an EAC xenograft model. The radiosensitizing effect of nimorazole was questionable and requires further investigation

There was movement that was stationary, for the four-velocity had passed around

Is the Doppler interpretation of galaxy redshifts in a Friedmann-Lemaitre-Robertson-Walker (FLRW) model valid in the context of the approach to comoving spatial sections pioneered by de Sitter, Friedmann, Lemaitre and Robertson, i.e. according to which the 3-manifold of comoving space is characterised by both its curvature and topology? Holonomy transformations for flat, spherical and hyperbolic FLRW spatial sections are proposed. By quotienting a simply-connected FLRW spatial section by an appropriate group of holonomy transformations, the Doppler interpretation in a non-expanding Minkowski space-time, obtained via four-velocity parallel transport along a photon path, is found to imply that an inertial observer is receding from herself at a speed greater than zero, implying contradictory world-lines. The contradiction in the multiply-connected case occurs for arbitrary redshifts in the flat and spherical cases, and for certain large redshifts in the hyperbolic case. The link between the Doppler interpretation of redshifts and cosmic topology can be understood physically as the link between parallel transport along a photon path and the fact that the comoving spatial geodesic corresponding to a photon's path can be a closed loop in an FLRW model of any curvature. Closed comoving spatial loops are fundamental to cosmic topology.Comment: 8 pages, 2 figures; v2: missing dot added to Defn 1, minor corrections; submitted to MNRA