SIMS MICROSCOPY: METHODOLOGY, PROBLEMS AND PERSPECTIVES IN MAPPING DRUGS AND NUCLEAR MEDICINE COMPOUNDS
Article first published online: 2 JAN 2013
© The Author(s) Journal compilation © 1997 International Federation for Cell Biology
Cell Biology International
Volume 21, Issue 10, pages 619–633, October 1997
How to Cite
CLERC, J., FOURRÉ, C. and FRAGU, P. (1997), SIMS MICROSCOPY: METHODOLOGY, PROBLEMS AND PERSPECTIVES IN MAPPING DRUGS AND NUCLEAR MEDICINE COMPOUNDS. Cell Biology International, 21: 619–633. doi: 10.1006/cbir.1998.0205
- Issue published online: 2 JAN 2013
- Article first published online: 2 JAN 2013
- Accepted 4 December 1997
- Cited By
- SIMS microscopy
Secondary ion mass spectrometry (SIMS) microscopy, a mass spectrometry method designed in the 1960s, offers new analytical capabilities, high sensitivity (ppm to ppb region), high specificity and improved lateral resolution, thus facilitating insight into many physiological and biomedical questions. Apart from the sample preparation and the physical characteristics of the detection, the biological model must also be considered.
SIMS analysis of diffusible ions and molecules requires strict cryogenic procedures which always begin by a flash-freeze fixation. Cellular integrity can be checked by mapping the major element distributions since intra and extracellular ions are redistributed only in damaged cells. Cryofixing may be followed either by a freeze-fracture methodology or by cryoembedding and dry-cutting. Chemical sample preparation is only used for ions or molecules bound to fixed cell structures.
The use of scanning procedures ameliorates the lateral resolution and chromosome imaging has been reported with probe size of below 50nm. Absolute quantification can be derived for embedded specimen by using internal references included in tissue equivalent resins. The sensitivity is limited by the ionization yield of the tag element and may be further impaired when working at high mass resolution (≥5000) to eliminate interfering cluster ions.
SIMS drug mapping is usually performed after in vitro administration of a molecule to cell culture systems. Drug detection is accomplished indirectly by detecting a tag isotope naturally present or introduced by labelling, mainly with halogens,15N and14C. Molecular imaging with TOF-SIMS is an appealing alternative especially for heavier compounds. We stress some biological problems through a critical review of published SIMS drug studies. SIMS proved useful in assessing the targeting specificity of nuclear medicine pharmaceutics, even after in vivo administration. The first microscopic evidence of a thionamide induced follicular blockade of the iodine organification process is presented in a human sample.