The synthesis of a new probe for PET imaging reporter gene HSV1‐tk: 2‐amino‐6‐[18F] fluoro‐9‐ (4‐hydroxy‐3‐hydroxymethylbutyl) purine (6‐[18F]fluoropenciclovir)

The one step radiosynthesis of 2‐amino‐6‐ [¹⁸F]fluoro‐9‐(4‐hydroxy‐3‐hydroxymethylbutyl) purine (6‐[¹⁸F]fluoropenciclovir) 6 is reported. Radiolabeled product 6‐[¹⁸F]fluoropenciclovir 6 was prepared by radiofluorination of compound 4 with [¹⁸F]KF and isolated by a silica Sep‐Pak cartridge. The radiochemical yield of compound 6 was 45–55% decay corrected (d.c.) in six runs with radiochemical purity >98% and the radiosynthesis time was 35–42 min from end of bombardment (EOB). Copyright © 2006 John Wiley & Sons, Ltd.     

Radiosynthesis of 3‐(3‐[18F]fluoropropoxy)‐4‐(benzyloxy)‐N‐[(1‐dimethylaminocyclopentyl)methyl]‐5‐methoxybenzamide,a potential PET radiotracer for the glycine transporter GlyT‐2

The recently described selective and potent GlyT2 antagonist, 4‐benzyloxy‐3,5‐dimethoxy‐N‐[(1‐dimethylaminocyclopentyl) methyl]benzamide (IC₅₀=16 nM) provided an important additional tool to further characterize GlyT2 pharmacology. In order to identify an effective PET radioligand for in vivo assessment of the GlyT‐2 transporter, 3‐(3‐[¹⁸F]fluoropropoxy)‐4‐(benzyloxy)‐N‐((1‐dimethylaminocyclopentyl) methyl)‐5‐methoxybenzamide ([¹⁸F] 3 ), a novel analog of 4‐benzyloxy‐3,5‐dimethoxy‐N‐[(1‐dimethylaminocyclopentyl) methyl]benzamide was synthesized using a one‐pot, two‐step method. The NCA radiofluorination of 1,3‐propanediol di‐p‐tosylate in the presence of K₂CO₃ and Kryptofix‐222 in acetonitrile gave 81% 3‐[¹⁸F]fluoropropyl tosylate, which was subsequently coupled with 4‐benzyloxy‐3‐hydroxy‐5‐methoxy‐N‐[(1‐dimethylaminocyclopentyl) methyl]benzamide in the same reaction vessel. Solvent extraction and HPLC (Eclipse XDB‐C8 column, 80/20/0.1 MeOH/H₂O/Et₃N, 3.0 ml/min) gave [¹⁸F] 3 in 98.5% radiochemical purity. The radiochemical yield was determined to be 14.0–16.2% at EOS, and the specific activity was 1462±342 GBq/µmol. The time of synthesis and purification was 128 min. The final product was prepared as a sterile saline solution suitable for in vivo use. Copyright © 2006 John Wiley & Sons, Ltd.     

硒锌制剂拮抗氟毒性作用的实验研究

为研究硒锌制剂对氟毒性的影响,大鼠在饮高氟水的同时给予硒锌制剂,结果发现硒锌制剂可通过促进尿氟排泄,增加GSH-Px和SOD活性及GSH含量而抑制氟引起的脂质过氧化,从而降低尿γ-GT活性和LPO水平.提示硒锌制剂对氟毒性具有明显的拮抗作用,其机理与促进尿氟排泄和抗脂质过氧化作用有关.     

应用Opalescence脱色方法治疗色素牙的疗效观察(附112例临床分析)

目的 :研究 Opalescence脱色方法对色素牙脱色的疗效。方法 :将 Opalescence脱色剂涂于个别托模唇、颊侧内 ,病人每晚睡前刷牙后擦干牙面 ,戴上托模 ,晨起摘下冲洗干净 ,每天 1次 ,疗程一般为 2周 ,视疗效及患者反应增减用药时间。结果 :1 1 2例患者脱色治疗后氟斑牙的显效率( 80 .8%)高于四环素牙的显效率 ( 66.7%)。有 2 3例病人疗效不甚满意。结论 :应用 Opalescence脱色治疗活髓色素牙效果明显 ,脱色后牙体呈自然色泽 ,透明感好 ,特别适用于年龄较轻、无牙体缺损的氟斑牙及四环素牙的脱色。     

19F-magnetic resonance spectroscopy and chemical shift imaging for schizophrenic patients using haloperidol decanoate

Haloperidol decanoate is widely used in the maintenance treatment of schizophrenia and other psychotic disorders, but knowledge concerning its pharmacokinetics at the injected region is very limited. Because the chemical structure of haloperidol contains fluorine, in vivo 19F-magnetic resonance (MR) spectroscopy (repetition time (TR) = 1 s) and chemical shift imaging (CSI; TR = 1 s, pixel size = 15 x 15 mm) were performed in schizophrenic patients who were treated with haloperidol decanoate (three men and one woman) to measure its diachronic change at the injection point and visualize its local distribution after intramuscular injection. 19F signals (T1 time = 365 ms) were obtained at the haloperidol decanoate-injected region. The decrease rate of the signal-to-noise ratio (SNR) by 19F-MR spectroscopy seemed large in comparison with that of the plasma haloperidol concentration. The distribution was clearly visualized by 19F-CSI for a few days after the injection, but after 1 week could no longer be seen. Although the slow-release characteristics of depot neuroleptics have been explained by the slow diffusion of esterified neuroleptics from the oil vehicle, this result may suggest that there are other mechanisms involved in maintaining the plasma haloperidol concentration. In vivo 19F-MR spectroscopy and CSI are potentially applicable for the pharmacokinetic analysis of haloperidol and other drugs containing fluorine in their structure.     

Initial evaluation of PET/CT with 18F‐FSU‐880 targeting prostate‐specific membrane antigen in prostate cancer patients

This first‐in‐man study was carried out to evaluate the safety, whole‐body distribution, dose estimation, and lesion accumulation of ¹⁸F‐FSU‐880, a newly developed probe targeting prostate‐specific membrane antigen. Six prostate cancer patients with known metastatic lesions underwent serial whole‐body PET/computed tomography (CT) with ¹⁸F‐FSU‐880. Blood and urine were analyzed before and after PET/CT. Accumulation of ¹⁸F‐FSU‐880 in organs and metastatic lesions in serial PET images were evaluated by measuring the standardized uptake values. From the biodistribution data, the organ doses and whole‐body effective dose were calculated using OLINDA/EXM software was developed by Dr. Michael Stabin of Vanderbilt University, Nashville, Tennessee, USA. ¹⁸F‐FSU‐880 PET/CT could be carried out without significant adverse effects. High physiological uptake was observed in the salivary/lachrymal glands and kidneys. The effective dose was calculated to be 0.921 × 10^?2 mSv/MBq. Known metastatic lesions were clearly visualized with high image contrast that increased with time, except in 1 patient, whose bone metastases were well‐controlled and inactive. The PET/CT with ¹⁸F‐FSU‐880 could be carried out safely and could clearly visualize active metastatic lesions. The present results warrant further clinical studies with a larger number of cases to verify the clinical utility of ¹⁸F‐FSU‐880 PET/CT in the management of prostate cancer patients.     

Synthesis of a phenolic precursor and its efficient O‐[18F]fluoroethylation with purified no‐carrier‐added [18F]2‐fluoroethyl brosylate as the labeling agent

[¹⁸F]2‐Fluoroethyl‐p‐toluenesulfonate also called [¹⁸F]2‐fluoroethyl tosylate has been widely used for labeling radioligands for positron emission tomography (PET). [¹⁸F]2‐Fluoroethyl‐4‐bromobenzenesulfonate, also called [¹⁸F]2‐fluoroethyl brosylate ([¹⁸F]F(CH₂)₂OBs), was used as an alternative radiolabeling agent to prepare [¹⁸F]FEOHOMADAM, a fluoroethoxy derivative of HOMADAM, by O‐fluoroethylating the phenolic precursor. Purified by reverse‐phase HPLC, the no‐carrier‐added [¹⁸F]F(CH₂)₂OBs was obtained in an average radiochemical yield (RCY) of 35%. The reaction of the purified and dried [¹⁸F]F(CH₂)₂OBs with the phenolic precursor was performed by heating in DMF and successfully produced [¹⁸F]FEOHOMADAM, after HPLC purification, in RCY of 21%. Copyright © 2013 John Wiley & Sons, Ltd.     

A concise radiosynthesis of the tau radiopharmaceutical, [18F]T807

Fluorine‐18 labeled 7‐(6‐fluoropyridin‐3‐yl)‐5H‐pyrido[4,3‐b]indole ([¹⁸F]T807) is a potent and selective agent for imaging paired helical filaments of tau and is among the most promising PET radiopharmaceuticals for this target in early clinical trials. The present study reports a simplified one‐step method for the synthesis of [¹⁸F]T807 that is broadly applicable for routine clinical production using a GE TRACERlab? FX_FN radiosynthesis module. Key facets of our optimized radiosynthesis include development and use of a more soluble protected precursor, tert‐butyl 7‐(6‐nitropyridin‐3‐yl)‐5H‐pyrido[4,3‐b]indole‐5‐carboxylate, as well as new HPLC separation conditions that enable a facile one‐step synthesis. During the nucleophilic fluorinating reaction with potassium cryptand [¹⁸F]fluoride (K[¹⁸F]/K₂₂₂) in DMSO at 130 °C over 10 min the precursor is concurrently deprotected. Formulated [¹⁸F]T807 was prepared in an uncorrected radiochemical yield of 14 ± 3%, with a specific activity of 216 ± 60 GBq/µmol (5837 ± 1621 mCi/µmol) at the end of synthesis (60 min; n = 3) and validated for human use. This methodology offers the advantage of faster synthesis in fewer steps, with simpler automation that we anticipate will facilitate widespread clinical use of [¹⁸F]T807. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis and evaluation of two fluorine‐18 labelled phenylbenzothiazoles as potential in vivo tracers for amyloid plaque imaging

Uncharged derivatives of thioflavin‐T have known in vitro and in vivo affinity for amyloid β. We synthesized and evaluated two derivatives with a fluorine‐18 labelled fluoropropoxy substituent either at the 6‐position or at the 2′‐position of the 2‐(4′‐aminophenyl)‐1,3‐benzothiazole core with the aim to get suitable radiotracers to perform amyloid plaque imaging. The fluorine‐18 labelled compounds were obtained by nucleophilic substitution of the corresponding tosyl precursors with [¹⁸F]fluoride with a radiochemical yield of 50%, yielding 6‐(3′′‐[¹⁸F]fluoropropoxy)‐2‐(4′‐aminophenyl)‐1,3‐benzothiazole ([¹⁸F]2) and 2‐[2′‐(3′′‐[¹⁸F]fluoropropoxy)‐4′‐aminophenyl]‐1,3‐benzothiazole ([¹⁸F]3) with a specific activity between 33 and 51 GBq/µmol. The identity of the radiolabelled compounds was confirmed using radio‐LC‐MS and by comparing retention times on RP‐HPLC. Biodistribution studies in healthy mice showed for both compounds a relatively high initial brain uptake, which was significantly higher for [¹⁸F]2 than for [¹⁸F]3 (4.5% ID/g versus 3.0% ID/g, p<0.05). Wash‐out from control brain was faster for [¹⁸F]3. In vitro binding affinity tests using human AD brain homogenates revealed that only compound 2 has affinity for fibrillar amyloid β (K_i=14.5 nM). This was confirmed by the incubation of transgenic APP mouse brain sections with the cold compounds, where 3 did not stain any structure whereas 2 stained amyloid plaques present in APP mouse brain. These data suggest that [¹⁸F]2 may be a useful tracer for in vivo visualization of fibrillar amyloid β. Copyright © 2009 John Wiley & Sons, Ltd.     

改水降氟10年后儿童氟负荷及氟效应指标的调查

目的 为评价改水降氟对地方性氟中毒的防治效果。方法 检测分析了（未改水）病区组、改水病区组、非病区组８～１２岁儿童的尿氟和氟毒性效应指标。结果 尿氟均值病区组明显高于改水病区组（Ｐ〈０．０１）和非病区组（Ｐ〈０．０１）;尿羟脯氨酸（ＨＯＰ）排泄量均值病区级亦明显高于改水病区组（Ｐ〈０．０１）和非病区组（Ｐ〈０．０１）;改水病区组８～１２岁儿童氟斑牙患病率由１０年前的８２．４％降至６．４５％,明显低