18F标记的苯乙烯基嘧啶类Aβ显像剂的制备与初步生物评价

为研发新型Aβ正电子显像剂,设计合成对甲苯磺酰氧基取代的苯乙烯基嘧啶化合物Boc-SPm2-OTs和Boc-SPm5-OTs,并通过亲核取代反应进行¹⁸F标记,得到¹⁸F-SPm2和¹⁸F-SPm5,放化纯度均大于99%。¹⁸F-SPm2和¹⁸F-SPm5均具有适宜的亲脂性（LogP=1~2.5）,在生理盐水中可稳定存在3 h以上,能选择性结合Aβ,但其亲和性较弱（K_i分别为246.6 nmol/L和318.2 nmol/L）,体内生物分布实验表明,两者初始脑放射性摄取均相对较高,但正常脑组织清除较慢,而且存在明显脱氟现象。初步的研究结果表明,¹⁸F-SPm2和¹⁸F-SPm5不是理想的Aβ显像剂,需要进行进一步的结构修饰以克服其缺点。     

Cover Feature: A Comparative Study of in vitro Assays for Predicting the Nonspecific Binding of PET Imaging Agents in vivo (ChemMedChem 7/2020)

Nonspecific binding (NSB) is a key parameter in optimizing PET imaging tracers. We compared the ability to predict NSB of three available methods: LIMBA, rat f_u,brain, and CHI(IAM). Even though NSB is often associated with lipophilicity, we observed that logD does not correlate with any of these assays, clearly indicating that lipophilicity, while influencing NSB, is insufficient to predict it. A cross-comparison of the methods showed that all three correlate and are useful predictors of NSB. The three assays, however, rank the molecules slightly differently, illustrating the challenge of comparing molecules within a narrow chemical space. We also noted that CHI(IAM) values more effectively predict V_NS, a measure of in vivo NSB in the human brain. CHI(IAM) measurements might be a closer model of the actual physicochemical interaction between PET tracer candidates and cell membranes, and seems to be the method of choice for the optimization of in vivo NSB.     

Sensitivity of positrons at hydrogen storage sites in FeCr alloy containing vacancy and helium atom

Here, the storage sites of hydrogen in FeCr alloy, namely (H, He)–V nano-clusters with open volume, have been investigated by first-principles calculations and positron annihilation spectroscopy. The positron lifetimes in the nano-clusters obtained by theoretical calculations and experiments were compared. These results suggest that positron is sensitive to the relative position of the gas atoms decorating the open volume; and a helium atom forms a more repulsive ion core than a hydrogen atom when it occupies the vacancy, resulting in a decrease in positron lifetime. Interpretation of the PAS data was successfully combined with theoretical calculations, and allowed us to determine the defect status in specimens after H/He irradiation with different implantation patterns. The speculated kinds of hydrogen storage sites formed after irradiation are summarized. For the He-ions pre-implanted situation, the helium-vacancy clusters or bubbles forming in advance may recombine with H atoms to form stable He–H–V complex.     

Click-Chemistry (CuAAC) Trimerization of an αvβ6 Integrin Targeting Ga-68-Peptide: Enhanced Contrast for in-Vivo PET Imaging of Human Lung Adenocarcinoma Xenografts

α_vβ₆ Integrin is an epithelial transmembrane protein that recognizes latency-associated peptide (LAP) and primarily activates transforming growth factor beta (TGF-β). It is overexpressed in carcinomas (most notably, pancreatic) and other conditions associated with α_vβ₆ integrin-dependent TGF-β dysregulation, such as fibrosis. We have designed a trimeric Ga-68-labeled TRAP conjugate of the α_vβ₆-specific cyclic pentapeptide SDM17 (cyclo[RGD-Chg-E]-CONH₂) to enhance α_vβ₆ integrin affinity as well as target-specific in-vivo uptake. Ga-68-TRAP(SDM17)₃ showed a 28-fold higher α_vβ₆ affinity than the corresponding monomer Ga-68-NOTA-SDM17 (IC₅₀ of 0.26 vs. 7.4 nM, respectively), a 13-fold higher IC₅₀-based selectivity over the related integrin α_vβ₈ (factors of 662 vs. 49), and a threefold higher tumor uptake (2.1 vs. 0.66 %ID/g) in biodistribution experiments with H2009 tumor-bearing SCID mice. The remarkably high tumor/organ ratios (tumor-to-blood 11.2; -to-liver 8.7; -to-pancreas 29.7) enabled high-contrast tumor delineation in PET images. We conclude that Ga-68-TRAP(SDM17)₃ holds promise for improved clinical PET diagnostics of carcinomas and fibrosis.     

两类压缩态光场的特性比较

本文指出光场压缩态|α,z〉A=S(z)D(α)|0〉和|α,z〉B=D(α)S(z)|0〉不完全等价,它们实质上是本文命名的压缩子(Squeezon)湮灭算符b=SaS~+的两个本征态,具有完全相同的压缩特性,但本征值不同,光子统计分布和光子统计特性有显著差异,所含的能量状况亦很不相同。     

价电子密度与Y123铜氧超导电性关系研究

通过X射线衍射、超导电性测试、氧含量变化、正电子湮没以及理论计算等方法,系统研究了金属离子掺杂的YBa2Cu3-x(Fe,Co,Al)xO7-δ(x=0.0~0.5)铜氧超导体的超导电性,为了比较也一并讨论了Zn掺杂样品的实验和理论结果。研究表明,超导转变温度Tc与样品中价电子密度无直接关联,与Hall实验揭示的Tc与空穴载流子浓度关系有同样结论,表明电声耦合机制在铜氧超导体中失效。因此,无论是空穴配对还是电子配对,仅仅是实现超导态的前提,并非其真正的决定因素。如果铜氧超导微观机制依然沿袭"电声耦合"理念很可能误入歧途。     

用正电子湮没技术研究硼在Ni3Al中的存在形式

本文用正电子湮没技术(PAT)研究了不同硼含量的单晶和多晶Ni_3Al中硼原子的存在形式。在Ni_3Al合金中加入少量硼(≤1.37％)时,一部分硼原子以间隙方式溶解到基体中,使晶格发生畸变,导致基体中正电子寿命(τ)增长;另一部分硼偏聚到空位型缺陷上,产生“填充效应”,导致平均寿命■和S参数下降。硼量为2.22at.-％时,缺陷态的τ显著增长,■和S参数增大,表明在晶界成晶内析出硼化物,诱发了较多的自由体积较大的缺陷。     

Free volume in two differently plasticized poly(vinyl chloride)s: a positron lifetime and PVT study

The temperature dependence of the specific volume, V, and of the mean size of local free volumes (holes), v_h, of poly(vinyl chloride) containing 10 wt% (PVC-h) and 30 wt% (PVC-s) of the plasticizer di-n-butyl phthalate (DBP) were studied by pressure-volume-temperature (PVT) and positron annihilation lifetime spectroscopy (PALS) experiments. Using the Simha-Somcynsky equation-of-state, the hole fraction h was calculated from the PVT data. It was found that the thermal expansivity of the specific volume V, the specific free volume V_f=hV, and v_h increase with the content of plasticizer. From the comparison of V and V_f with v_h the hole number per gram N′_h is estimated. Other than v_h, N′_h does not depend on the temperature nor on the content of plasticizer.     

11C‐ and 18F‐Labeled Radioligands for P‐Glycoprotein Imaging by Positron Emission Tomography

P‐Glycoprotein (P‐gp) is an efflux transporter widely expressed at the human blood–brain barrier. It is involved in xenobiotics efflux and in onset and progression of neurodegenerative disorders. For these reasons, there is great interest in the assessment of P‐gp expression and function by noninvasive techniques such as positron emission tomography (PET). Three radiolabeled aryloxazole derivatives: 2‐[2‐(2‐methyl‐(¹¹C)‐5‐methoxyphenyl)oxazol‐4‐ylmethyl]‐6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinoline ([¹¹C]‐ 5 ); 2‐[2‐(2‐fluoromethyl‐(¹⁸F)‐5‐methoxyphenyl)oxazol‐4‐ylmethyl]‐6,7‐dimethoxy‐1,2,3,4‐tetra‐hydroisoquinoline ([¹⁸F]‐ 6 ); and 2‐[2‐(2‐fluoroethyl‐(¹⁸F)‐5‐methoxyphenyl)oxazol‐4‐ylmethyl]‐6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinoline ([¹⁸F]‐ 7 ), were tested in several in vitro biological assays to assess the effect of the aryl substituent in terms of potency and mechanism of action toward P‐gp. Methyl derivative [¹¹C]‐ 5 is a potent P‐gp substrate, whereas the corresponding fluoroethyl derivative [¹⁸F]‐ 7 is a P‐gp inhibitor. Fluoromethyl compound [¹⁸F]‐ 6 is classified as a non‐transported P‐gp substrate, because its efflux increases after cyclosporine A modulation. These studies revealed a promising substrate and inhibitor, [¹¹C]‐ 5 and [¹⁸F]‐ 7 , respectively, for in vivo imaging of P‐gp by using PET.     

The influence of acrylic acid groups on the microstructure of HDPE/BT system studied by positron annihilation

Two types of composites, high‐density polyethylene (HDPE)/Bentonite (BT) and high‐density polyethylene grafted with acrylic acid (HDPE‐g‐AA)/(BT), are prepared by melt compounding. The microstructure of the composite has been studied by the means of positron annihilation lifetime spectroscopy (PALS). It has been found that the mean free volume size is nearly the same in composites and HDPE matrices with different BT concentration. While the ortho‐positronium (o‐Ps) intensity decreased for HDPE‐g‐AA and its lifetime distribution is narrower than that for pure HDPE. With the increasing of BT content, the o‐Ps intensity increases for HDPE‐g‐AA/BT composites and the o‐Ps intensity decreases for HDPE/BT composites. It is found that the carboxyl group of Acrylic acid plays a significant chemical inhibition on positronium formation. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008