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加速器质谱法在原子水平上的同位素测量的生物医学应用。

Biomedical applications of accelerator mass spectrometry-isotope measurements at the level of the atom.

作者信息

Barker J, Garner R C

机构信息

Centre for Biomedical Accelerator Mass Spectrometry Ltd., York, UK.

出版信息

Rapid Commun Mass Spectrom. 1999;13(4):285-93. doi: 10.1002/(SICI)1097-0231(19990228)13:4<285::AID-RCM469>3.0.CO;2-R.

DOI:10.1002/(SICI)1097-0231(19990228)13:4<285::AID-RCM469>3.0.CO;2-R
PMID:10097404
Abstract

Accelerator mass spectrometry (AMS) is a nuclear physics technique developed about twenty years ago, that uses the high energy (several MeV) of a tandem Van de Graaff accelerator to measure very small quantities of rare and long-lived isotopes. Elements that are of interest in biomedicine and environmental sciences can be measured, often to parts per quadrillion sensitivity, i.e. zeptomole to attomole levels (10(-21)-10(-18) mole) from milligram samples. This is several orders of magnitude lower than that achievable by conventional decay counting techniques, such as liquid scintillation counting (LSC). AMS was first applied to geochemical, climatological and archaeological areas, such as for radiocarbon dating (Shroud of Turin), but more recently this technology has been used for bioanalytical applications. In this sphere, most work has been conducted using aluminium, calcium and carbon isotopes. The latter is of special interest in drug metabolism studies, where a Phase 1 adsorption, distribution, metabolism and excretion (ADME) study can be conducted using only 10 nanoCurie (37 Bq or ca. 0.9 microSv) amounts or less of 14C-labelled drugs. In the UK, these amounts of radioactivity are below those necessary to request specific regulatory approval from the Department of Health's Administration of Radioactive Substances Advisory Committee (ARSAC), thus saving on valuable development time and resources. In addition, the disposal of these amounts is much less an environmental issue than that associated with microCurie quantities, which are currently used. Also, AMS should bring an opportunity to conduct "first into man" studies without the need for widespread use of animals. Centre for Biomedical Accelerator Mass Spectrometry (CBAMS) Ltd. is the first fully commercial company in the world to offer analytical services using AMS. With its high throughput and relatively low costs per sample analysis, AMS should be of great benefit to the pharmaceutical and biotechnology industries as well as other life science areas.

摘要

加速器质谱法(AMS)是大约二十年前开发的一种核物理技术,它利用串联范德格拉夫加速器的高能量(几兆电子伏特)来测量极少量的稀有和长寿命同位素。生物医学和环境科学中感兴趣的元素都可以被测量,通常能达到千万亿分之一的灵敏度,即从毫克样品中检测出zeptomole到attomole水平(10^(-21)-10^(-18)摩尔)。这比传统的衰变计数技术,如液体闪烁计数(LSC)所能达到的灵敏度低几个数量级。AMS最初应用于地球化学、气候学和考古学领域,比如用于放射性碳年代测定(都灵裹尸布),但最近这项技术已被用于生物分析应用。在这个领域,大多数工作是使用铝、钙和碳同位素进行的。后者在药物代谢研究中特别受关注,在药物代谢研究中,仅使用10纳居里(37贝可勒尔或约0.9微希沃特)或更少的14C标记药物就可以进行一期吸收、分布、代谢和排泄(ADME)研究。在英国,这些放射性物质的量低于向卫生部放射性物质咨询委员会(ARSAC)申请特定监管批准所需的量,从而节省了宝贵的研发时间和资源。此外,与目前使用的微居里量相比,这些量的放射性物质的处置对环境的影响要小得多。而且,AMS应该会带来一个无需广泛使用动物就能进行“首次人体”研究的机会。生物医学加速器质谱中心(CBAMS)有限公司是世界上第一家提供使用AMS分析服务的完全商业化公司。凭借其高通量和相对较低的每份样品分析成本,AMS应该会给制药和生物技术行业以及其他生命科学领域带来巨大益处。

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