SIMS MICROSCOPY - METHODOLOGY, PROBLEMS AND PERSPECTIVES IN MAPPING DRUGS AND NUCLEAR-MEDICINE COMPOUNDS

Secondary ion mass spectrometry (SIMS) microscopy, a mass spectrometry method designed in the 1960s, offers new analytical capabilities, hig h sensitivity (ppm to ppb region), high specificity and improved later al resolution, thus facilitating insight into many physiological and b iomedical questions. Apart from the sample preparation and the physica l characteristics of the detection, the biological model must also be considered. SIMS analysis of diffusible ions and molecules requires st rict cryogenic procedures which always begin by a flash-freeze fixatio n. Cellular integrity can be checked by mapping the major element dist ributions 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 prep aration is only used for ions or molecules bound to fixed cell structu res, The use of scanning procedures ameliorates the lateral resolution and chromosome imaging has been reported with probe size of below 50 nm. Absolute quantification can be derived for embedded specimen by us ing internal references included in tissue equivalent resins. The sens itivity is limited by the ionization yield of the tag element and may be further impaired when working at high mass resolution (greater than or equal to 5000) to eliminate interfering cluster ions. SIMS drug ma pping 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,N-15 and C-14. Molecular imaging with TOF-SIMS i s an appealing alternative especially for heavier compounds. We stress some biological problems through a critical review of published SIR I S drug studies. SIMS proved useful in assessing the targeting specific ity of nuclear medicine pharmaceutics, even after in vivo administrati on. The first microscopic evidence of a thionamide induced follicular blockade of the iodine organification process is presented in a human sample. (C) 1997 Academic Press.