Preclinical Applications of 3'-Deoxy-3'-[18F]Fluorothymidine in Oncology - A Systematic Review

The positron emission tomography (PET) tracer 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) has been proposed to measure cell proliferation non-invasively in vivo. Hence, it should provide valuable information for response assessment to tumor therapies. To date, [18F]FLT uptake has found limited use as a response biomarker in clinical trials in part because a better understanding is needed of the determinants of [18F]FLT uptake and therapy-induced changes of its retention in the tumor. In this systematic review of preclinical [18F]FLT studies, comprising 174 reports, we identify the factors governing [18F]FLT uptake in tumors, among which thymidine kinase 1 plays a primary role. The majority of publications (83 %) report that decreased [18F]FLT uptake reflects the effects of anticancer therapies. 144 times [18F]FLT uptake was related to changes in proliferation as determined by ex vivo analyses. Of these approaches, 77 % describe a positive relation, implying a good concordance of tracer accumulation and tumor biology. These preclinical data indicate that [18F]FLT uptake holds promise as an imaging biomarker for response assessment in clinical studies. Understanding of the parameters which influence cellular [18F]FLT uptake and retention as well as the mechanism of changes induced by therapy is essential for successful implementation of this PET tracer. Hence, our systematic review provides the background for the use of [18F]FLT in future clinical studies

The effect of flower-like tatania towards characteristics and performance of polysulfone mixed matrix membrane

For ages, the polymeric membrane such as PSf is widely used in liquid separation for various application as the polymer itself offer versatile and attractive properties. However, due to strong hydrophobic nature of PSf property that create serious fouling problem to most of the separation process, thus modification of membrane by integrating strong hydrophilic particles is always practically used among industries and researchers. In this research, the effect of FLT as an additive in the PSf membrane was investigated. With consideration of the FLT that offer larger specific surface area as compared to ST that able to generate better performances and properties of polymer MMM. In this work, the polymer MMM of PSf/FLT and PSf/ST membranes were prepared via phase inversion method at five different concentrations of additive. Membrane characterization involved several observations such as cross-section area, particle distribution, surface roughness, hydrophilicity property, mean pore size, mechanical strength and porosity. Meanwhile, membrane performances were evaluated in terms of HA rejection, PWF, antifouling, antibacterial activity and photocatalytic properties based on self-cleaning antifouling efficiency. From the result, the addition of FLT was strongly influenced overall structure and characteristics of the membrane compared to ST. With a larger surface area of FLT and homogenous distribution inside membrane structure have resulted in better hydrophilicity effect thus improved the membrane performances. The PWF result was increased from 61.33 L/m2h to 137.81 L/m2h for PSf/ST and 155.46 L/m2h for PSf/FLT as increased additive to 3 wt%. Same results were obtained by rejection analysis where the PSf/FLT membrane able to reject more than 96% of HA and improved antifouling and self-cleaning efficiency. It is clearly shown that the present of higher specific surface area of FLT has improved overall characteristics and performances of the membrane compared to ST especially at 3 wt% of concentration

Repeatability of quantitative18F-FLT uptake measurements in solid tumors: an individual patient data multi-center meta-analysis

INTRODUCTION: 3'-deoxy-3'-[18F]fluorothymidine (18F-FLT) positron emission tomography (PET) provides a non-invasive method to assess cellular proliferation and response to antitumor therapy. Quantitative18F-FLT uptake metrics are being used for evaluation of proliferative response in investigational setting, however multi-center repeatability needs to be established. The aim of this study was to determine the repeatability of18F-FLT tumor uptake metrics by re-analyzing individual patient data from previously published reports using the same tumor segmentation method and repeatability metrics across cohorts. METHODS: A systematic search in PubMed, EMBASE.com and the Cochrane Library from inception-October 2016 yielded five18F-FLT repeatability cohorts in solid tumors.18F-FLT avid lesions were delineated using a 50% isocontour adapted for local background on test and retest scans. SUVmax, SUVmean, SUVpeak, proliferative volume and total lesion uptake (TLU) were calculated. Repeatability was assessed using the repeatability coefficient (RC = 1.96 × SD of test-retest differences), linear regression analysis, and the intra-class correlation coefficient (ICC). The impact of different lesion selection criteria was also evaluated. RESULTS: Images from four cohorts containing 30 patients with 52 lesions were obtained and analyzed (ten in breast cancer, nine in head and neck squamous cell carcinoma, and 33 in non-small cell lung cancer patients). A good correlation was found between test-retest data for all18F-FLT uptake metrics (R2 ≥ 0.93; ICC ≥ 0.96). Best repeatability was found for SUVpeak(RC: 23.1%), without significant differences in RC between different SUV metrics. Repeatability of proliferative volume (RC: 36.0%) and TLU (RC: 36.4%) was worse than SUV. Lesion selection methods based on SUVmax ≥ 4.0 improved the repeatability of volumetric metrics (RC: 26-28%), but did not affect the repeatability of SUV metrics. CONCLUSIONS: In multi-center studies, differences ≥ 25% in18F-FLT SUV metrics likely represent a true change in tumor uptake. Larger differences are required for FLT metrics comprising volume estimates when no lesion selection criteria are applied

Is Fecal Leukocyte Test a good predictor of Clostridium difficile associated diarrhea?

BACKGROUND: Fecal leukocyte test (FLT) is widely used to screen for invasive diarrheas including C. difficile associated diarrhea (CDAD), which account for more than 25 % of all antibiotic associated diarrhea. METHOD: 263 stool samples from patients with suspected CDAD were studied simultaneously for fecal leukocyte test (FLT) and Clostridium difficile toxin assay (CDTA). FLT was performed by the Giemsa technique and CDTA was performed by enzyme immuno assay (EIA). RESULTS: Sensitivity, specificity, positive predictive value and negative predictive value of FLT as compared to CDTA were 30%, 74.9%, 13.2% and 89.3% respectively. CONCLUSION: Considering the poor sensitivity of FLT, and the comparable cost and time of obtaining a CDTA at our institution, we conclude that FLT is not a good screening test for CDAD. Possible reasons for FLT being a poor predictor of CDTA are discussed