Platinum antitumour agents: A review of (bio)analysis

This paper summarizes analytical techniques in order to get a clear picture of the ins and outs of the (bio)analysis of platinum-containing compounds. The antitumour agent cisplatin has become an indispensable drug for the cure of a variety of cancer diseases. Since its introduc-tion in the early seventies, about 2,000 related platinum complexes were designed to devoid the dose-limiting nephrotoxicity. Some of them were introduced for clinical trial, such as carboplatin and iproplatin. To investigate the mechanism of action and pharmaco-kinetic behaviour, several interesting assays for total and specific platinum determination in biological matrices have been developed, each with its own possibilities and limitations.     

^99mTc—PYM一步法药盒的研制

研制适宜临床使用的肿瘤阳性显像剂９９ｍＴｃ平阳霉素（ＰＹＭ）一步法药盒，将药盒中含有的各种组分以适宜的配比和方法分装在小瓶中，避光，真空干燥，密封保存。结果：该药盒无菌，无热原，无毒副作用，标记产物的放化纯度大于９０％，稳定性在４小时以上。临床试用于肺癌等９６例患者，表明该药盒的标记方法简便易行，可用于临床上肺癌的诊断。     

Electrochemical nucleophilic synthesis of di-tert-butyl-(4-[18F]fluoro-1,2-phenylene)-dicarbonate

An electrochemical method with the ability to conduct ¹⁸F-fluorination of aromatic molecules through direct nucleophilic fluorination of cationic intermediates is presented in this paper. The reaction was performed on a remote-controlled automatic platform. Nucleophilic electrochemical fluorination of tert-butyloxycarbonyl (Boc) protected catechol, an intermediate model molecule for the positron emission tomography (PET) probe (3,4-dihydroxy-6-[¹⁸F]fluoro-l-phenylalanine), was performed. Fluorination was achieved under potentiostatic anodic oxidation in acetonitrile containing Et₃N·3HF and other supporting electrolytes. Radiofluorination efficiency was influenced by a number of variables, including the concentration of the precursor, concentration of Et₃N·3HF, type of supporting electrolyte, temperature and time, as well as applied potentials. Radio-fluorination efficiency of 10.4±0.6% (n=4) and specific activity of up to 43 GBq/mmol was obtained after 1 h electrolysis of 0.1 M of 4-tert-butyl-diboc-catechol in the acetonitrile solution of Et₃N·3HF (0.033 M) and NBu₄PF₆ (0.05 M). Density functional theory (DFT) was employed to explain the tert-butyl functional group facilitation of electrochemical oxidation and subsequent fluorination.     

心肌灌注显像剂^99mTc—tetrofosmin的制备和实验研究

进行新型心肌灌注显像剂ｔｅｔｒｏｆｏｓｍｉｎ的化学合成、药盒制备、９９ｍＴｃ标记、质量控制以及药理研究。方法：有机合成显像剂配体ｔｅｔｒｏｆｏｓｍｉｎ，正交实验确定９９ｍＴｃ标记药盒组分及配比，测定药盒及９９ｍＴｃｔｅｔｒｏｆｏｓｍｉｎ的理化性质，并通过药理实验确定其生物性能和安全性。Ｔｅｔｒｏｆｏｓｍｉｎ合成产物经１ＨＮＭＲ证实并制成药盒；该药盒经与９９ｍＴｃＯ－４混合，室温放置２０分钟后，可得到放化纯度大于９０％的９９ｍＴｃｔｅｔｒｏｆｏｍｉｎ，标记方法简便，标记产物稳定性好；小鼠分布实验显示较高的心／肝、心／肺比（６０分钟分别为４２６±２００和８９７±３２６）及较快的血清除速率（注射后２分钟全血百分注射剂量小于５％）；药盒各项技术指标符合药典体内诊断试剂的规定。结果表明，所研制的９９ｍＴｃｔｅｔｒｏｆｏｓｍｉｎ及其药盒达到临床试用质量。     

Highlights of the European Association of Nuclear Medicine Congress,Athens, Greece, 30 September to 4 October 2006

The 2006 EANM Congress, held in Athens, Greece, was once again a major event in the nuclear medicine scientific and educational calendar. The scientific programme, which included the second biennial ISRTRD meeting, confirmed the major developments taking place in (1) the diagnostic and prognostic uses of nuclear medicine imaging (both in PET and in single-photon studies), (2) radionuclide therapies, (3) radiochemistry and radiopharmacy, and (4) physics. This paper outlines the major findings in each of these areas.     

~3H-花生四烯酸参入大肠杆菌膜检测细胞内外磷脂酶A_2活性

目的　建立一种用同一底物检测分泌型磷脂酶A2 (sPLA2 )和胞浆型磷脂酶A2 (cPLA2 )的放射化学方法。方法　用3 H 花生四烯酸参入大肠杆菌膜 ,在一定条件下被待测PLA2 水解 ,以水解率的大小表示酶活性的高低。结果　测定cPLA2 和sPLA2 反应体系中最适pH值分别是 7.8和 8 0 ,最适钙离子浓度是 5和 13mmol/L ;cPLA2 批内CV 5 .2 % ,批间CV 10 .9% ,sPLA2 则分别是 4.9%和 7.8% ;倍比稀释实验结果具有良好的线性关系 ;急性胆囊炎患者血清sPLA2 活性明显高于正常人 ,内毒素 (LPS)诱导前后白血病K5 62细胞内和培养液中PLA2 活性差异有显著性 (P <0 .0 5 )。结论建立的检测法可满足临床和科研要求     

Strategies for PET imaging of the receptor for advanced glycation endproducts (RAGE)

The implication of the receptor for advanced glycation end-products (RAGE) in numerous diseases and neurodegenerative disorders makes it interesting both as a therapeutic target and as an inflammatory biomarker. In the context of investigating RAGE as a biomarker, there is interest in developing radiotracers that will enable quantification of RAGE using positron emission tomography (PET) imaging. We have synthesized potential small molecule radiotracers for both the intracellular ([¹⁸F]InRAGER) and extracellular ([¹⁸F]RAGER) domains of RAGE. Herein we report preclinical evaluation of both using in vitro (lead panel screens) and in vivo (rodent and nonhuman primate PET imaging) methods. Both radiotracers have high affinity for RAGE and show good brain uptake, but suffer from off-target binding. The source of the off-target PET signal is not attributable to binding to melatonin receptors, but remains unexplained. We have also investigated use of lipopolysaccharide (LPS)-treated mice as a possible animal model with upregulated RAGE for evaluation of new imaging agents. Immunoreactivity of the mouse brain sections revealed increases in RAGE in the male cohorts, but no difference in the female groups. However, it proves challenging to quantify the changes in RAGE due to off-target binding of the radiotracers. Nevertheless, they are appropriate lead scaffolds for future development of 2nd generation RAGE PET radiotracers because of their high affinity for the receptor and good CNS penetration.     

Capturing [11C]CO2 for use in aqueous applications

We present a simple method for trapping [¹¹C]CO₂ gas and releasing it into a buffered solution using an ion-exchange cartridge. Sodium hydroxide cartridges captured >99% of [¹¹C]CO₂ following NaOH activation. A sodium bicarbonate solution eluted >99% of trapped radioactivity. Trapping [¹¹C]CO₂ directly in small volumes of several solutions was less effective than cartridge methods. The recommended methods allow for fast and simple production of highly concentrated carbon-11 containing aqueous solutions for use in filling phantoms, calibrating detectors, or (bio)geochemical experiments.