Zusammenfassung
Platinum complexes are used for the treatment of several types of cancer. High platinum concentrations in the target tissue and low concentrations in dose-limiting tissue structures such as renal tubules are desirable to assure selective toxicity. Microlocal analysis of platinum distribution in tissue sections may thus contribute to the optimization of platinum therapy. Scanning laser ablation ...
Zusammenfassung
Platinum complexes are used for the treatment of several types of cancer. High platinum concentrations in the target tissue and low concentrations in dose-limiting tissue structures such as renal tubules are desirable to assure selective toxicity. Microlocal analysis of platinum distribution in tissue sections may thus contribute to the optimization of platinum therapy. Scanning laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was used to produce images of element distribution in 14-mu m thin sections of kidney tissue from a mouse treated with cis-platin 60 min prior to victimization. The sample surface was scanned (raster area 300 mm(2)) with a focused laser beam (wavelength 266 nm, diameter of laser crater 50 mu m, inter line distance 50 mu m and laser power density 3 x 10(9) W cm(-2)) in a cooled laser ablation chamber (about - 15 degrees C) developed for these measurements. The laser ablation system was coupled to a double-focusing sector field ICP-MS. Ion intensities of Cu-63(+), Zn-64(+), and Pt-196(+) were measured within the tissue by LA-ICP-MS. Matrix-matched laboratory standards served for calibration of analytical data. The mass spectrometric analysis yielded an inhomogeneous distribution for Cu, Zn, and Pt in thin kidney sections. Copper was enriched in the capsule and outer cortex, zinc in the inner cortex and the platinum concentration followed a centripetal gradient with clear medullar enrichment. Thus, scanning LA-ICP-MS may be a useful tool in the preclinical development of new and less nephrotoxic platinum complexes. (C) 2006 Elsevier B.V. All rights reserved.
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