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

Measurement of proton electromagnetic form factors in e+e−→ppˉe^+e^- \to p\bar{p} in the energy region 2.00-3.08 GeV

The process of $e^+e^- \rightarrow p\bar{p}$ is studied at 22 center-of-mass energy points ($\sqrt{s}$) from 2.00 to 3.08 GeV, exploiting 688.5~pb$^{-1}$ of data collected with the BESIII detector operating at the BEPCII collider. The Born cross section~($\sigma_{p\bar{p}}$) of $e^+e^- \rightarrow p\bar{p}$ is measured with the energy-scan technique and it is found to be consistent with previously published data, but with much improved accuracy. In addition, the electromagnetic form-factor ratio ($|G_{E}/G_{M}|$) and the value of the effective ($|G_{\rm{eff}}|$), electric ($|G_E|$) and magnetic ($|G_M|$) form factors are measured by studying the helicity angle of the proton at 16 center-of-mass energy points. $|G_{E}/G_{M}|$ and $|G_M|$ are determined with high accuracy, providing uncertainties comparable to data in the space-like region, and $|G_E|$ is measured for the first time. We reach unprecedented accuracy, and precision results in the time-like region provide information to improve our understanding of the proton inner structure and to test theoretical models which depend on non-perturbative Quantum Chromodynamics

Search for the decay J/ψ→γ+invisibleJ/\psi\to\gamma + \rm {invisible}

We search for $J/\psi$ radiative decays into a weakly interacting neutral particle, namely an invisible particle, using the $J/\psi$ produced through the process $\psi(3686)\to\pi^+\pi^-J/\psi$ in a data sample of $(448.1\pm2.9)\times 10^6$ $\psi(3686)$ decays collected by the BESIII detector at BEPCII. No significant signal is observed. Using a modified frequentist method, upper limits on the branching fractions are set under different assumptions of invisible particle masses up to 1.2 $\mathrm{\ Ge\kern -0.1em V}/c^2$. The upper limit corresponding to an invisible particle with zero mass is 7.0$\times 10^{-7}$ at the 90\% confidence level

First observations of hc→h_c \to hadrons

Based on $(4.48 \pm 0.03) \times 10^{8}$ $\psi(3686)$ events collected with the BESIII detector, five $h_c$ hadronic decays are searched for via process $\psi(3686) \to \pi^0 h_c$. Three of them, $h_c \to p \bar{p} \pi^+ \pi^-$, $\pi^+ \pi^- \pi^0$, and $2(\pi^+ \pi^-) \pi^0$ are observed for the first time, with statistical significances of 7.4$\sigma$, $4.9\sigma$, and 9.1$\sigma$, and branching fractions of $(2.89\pm0.32\pm0.55)\times10^{-3}$, $(1.60\pm0.40\pm0.32)\times10^{-3}$, and $(7.44\pm0.94\pm1.56)\times10^{-3}$, respectively, where the first uncertainties are statistical and the second systematic. No significant signal is observed for the other two decay modes, and the corresponding upper limits of the branching fractions are determined to be $B(h_c \to 3(\pi^+ \pi^-) \pi^0)<8.7\times10^{-3}$ and $B(h_c \to K^+ K^- \pi^+ \pi^-)<5.8\times10^{-4}$ at 90% confidence level.Comment: 17 pages, 16 figure

Precise Measurements of Branching Fractions for Ds+D_s^+ Meson Decays to Two Pseudoscalar Mesons

We measure the branching fractions for seven $D_{s}^{+}$ two-body decays to pseudo-scalar mesons, by analyzing data collected at $\sqrt{s}=4.178\sim4.226$ GeV with the BESIII detector at the BEPCII collider. The branching fractions are determined to be $\mathcal{B}(D_s^+\to K^+\eta^{\prime})=(2.68\pm0.17\pm0.17\pm0.08)\times10^{-3}$, $\mathcal{B}(D_s^+\to\eta^{\prime}\pi^+)=(37.8\pm0.4\pm2.1\pm1.2)\times10^{-3}$, $\mathcal{B}(D_s^+\to K^+\eta)=(1.62\pm0.10\pm0.03\pm0.05)\times10^{-3}$, $\mathcal{B}(D_s^+\to\eta\pi^+)=(17.41\pm0.18\pm0.27\pm0.54)\times10^{-3}$, $\mathcal{B}(D_s^+\to K^+K_S^0)=(15.02\pm0.10\pm0.27\pm0.47)\times10^{-3}$, $\mathcal{B}(D_s^+\to K_S^0\pi^+)=(1.109\pm0.034\pm0.023\pm0.035)\times10^{-3}$, $\mathcal{B}(D_s^+\to K^+\pi^0)=(0.748\pm0.049\pm0.018\pm0.023)\times10^{-3}$, where the first uncertainties are statistical, the second are systematic, and the third are from external input branching fraction of the normalization mode $D_s^+\to K^+K^-\pi^+$. Precision of our measurements is significantly improved compared with that of the current world average values

Meningeal lymphatic endothelial cells fulfill scavenger endothelial cell function and cooperate with microglia in waste removal from the brain

Brain lymphatic endothelial cells (BLECs) constitute a group of loosely connected endothelial cells that reside within the meningeal layer of the zebrafish brain without forming a vascular tubular system. BLECs have been shown to readily endocytose extracellular cargo molecules from the brain parenchyma, however, their functional relevance in relation to microglia remains enigmatic. We here compare their functional uptake efficiency for several macromolecules and bacterial components with microglia in a qualitative and quantitative manner in 5-day-old zebrafish embryos. We find BLECs to be significantly more effective in the uptake of proteins, polysaccharides and virus particles as compared to microglia, while larger particles like bacteria are only ingested by microglia but not by BLECs, implying a clear distribution of tasks between the two cell types in the brain area. In addition, we compare BLECs to the recently discovered scavenger endothelial cells (SECs) of the cardinal vein and find them to accept an identical set of substrate molecules. Our data identifies BLECs as the first brain-associated SEC population in vertebrates, and demonstrates that BLECs cooperate with microglia to remove particle waste from the brain.Thrombosis and Hemostasi

Improved measurements of the absolute branching fractions of the inclusive decays D+ (0) &#8594;&#966;X

By analyzing 2.93 fb-1 of e+e- annihilation data taken at the center-of-mass energy s=3.773 GeV with the BESIII detector, we determine the branching fractions of the inclusive decays D+→φX and D0→φX to be (1.135±0.034±0.031)% and (1.091±0.027±0.035)%, respectively, where X denotes any possible particle combination. The first uncertainties are statistical, and the second are systematic. We also determine the branching fractions of the decays D→φX and their charge conjugate modes D→φX separately for the first time, and no significant CP asymmetry is observed

Search for an invisible muon philic scalar X0X_{0} or vector X1X_{1} via J/ψ→μ+μ−+invisibleJ/\psi\to\mu^+\mu^-+\rm{invisible} decay at BESIII

A light scalar $X_{0}$ or vector $X_{1}$ particles have been introduced as a possible explanation for the $(g-2)_{\mu}$ anomaly and dark matter phenomena. Using $(8.998\pm 0.039)\times10^9$ \jpsi events collected by the BESIII detector, we search for a light muon philic scalar $X_{0}$ or vector $X_{1}$ in the processes $J/\psi\to\mu^+\mu^- X_{0,1}$ with $X_{0,1}$ invisible decays. No obvious signal is found, and the upper limits on the coupling $g_{0,1}'$ between the muon and the $X_{0,1}$ particles are set to be between $1.1\times10^{-3}$ and $1.0\times10^{-2}$ for the $X_{0,1}$ mass in the range of $1<M(X_{0,1})<1000$~MeV$/c^2$ at 90$\%$ confidence level.Comment: 9 pages 7 figure

Study of the Decays Ds+→KS0K+D_{s}^{+} \rightarrow K_{S}^{0}K^{+} and KL0K+K_{L}^{0}K^{+}

Using an $e^{+}e^{-}$ annihilation data sample corresponding to an integrated luminosity of $3.19~\mathrm{fb}^{-1}$ and collected at a center-of-mass energy $\sqrt{s} = 4.178~\mathrm{GeV}$ with the BESIII detector, we measure the absolute branching fractions $\mathcal{B}(D_{s}^{+} \rightarrow K_{S}^{0}K^{+}) = (1.425\pm0.038_{\rm stat.}\pm0.031_{\rm syst.})\%$ and $\mathcal{B}(D_{s}^{+} \rightarrow K_{L}^{0}K^{+}) =(1.485\pm0.039_{\rm stat.}\pm0.046_{\rm syst.})\%$. The branching fraction of $D_{s}^{+} \rightarrow K_{S}^{0}K^{+}$ is compatible with the world average and that of $D_{s}^{+} \rightarrow K_{L}^{0}K^{+}$ is measured for the first time. We present the first measurement of the $K_{S}^{0}$-$K_{L}^{0}$ asymmetry in the decays $D_{s}^{+} \rightarrow K_{S,L}^{0}K^{+}$, and $R(D_{s}^{+} \rightarrow K_{S,L}^{0}K^{+})=\frac{\mathcal{B}(D_{s}^{+} \rightarrow K_{S}^{0}K^{+}) -\mathcal{B}(D_{s}^{+} \rightarrow K_{L}^{0}K^{+})}{\mathcal{B}(D_{s}^{+} \rightarrow K_{S}^{0}K^{+}) +\mathcal{B}(D_{s}^{+} \rightarrow K_{L}^{0}K^{+})}= (-2.1\pm1.9_{\rm stat.}\pm1.6_{\rm syst.})\%$. In addition, we measure the direct $CP$ asymmetries $A_{\rm CP}(D_{s}^{\pm} \rightarrow K_{S}^{0}K^{\pm}) = (0.6\pm2.8_{\rm stat.}\pm0.6_{\rm syst.})\%$ and $A_{\rm CP}(D_{s}^{\pm} \rightarrow K_{L}^{0}K^{\pm}) = (-1.1\pm2.6_{\rm stat.}\pm0.6_{\rm syst.})\%$