Ultra-structural cell distribution of the melanoma marker iodobenzamide: improved potentiality of SIMS imaging in life sciences

The characteristics of the instrument are briefly described and an example of application is given. This example deals with the intracellular localization of an iodo-benzamide used as a diagnostic tool for the scintigraphic detection of melanic cells (e.g. metastasis of malignant melanoma). B16 melanoma cells were injected intravenously to C57BL6/J1/co mice. Multiple B16 melanoma colonies developed in the lungs of treated animals within three weeks. Iodobenzamide was injected intravenously in tumour bearing mice six hours before sacrifice. Small pieces of lung were prepared for SIMS analysis.Mouse lung B16 melanoma colonies were observed with high lateral resolution. Cyanide ions gave "histological" images of the cell, representative of the distribution of C and N containing molecules (e.g. proteins, nucleic acids, melanin, etc.) while phosphorus ions are mainly produced by nucleic acids. Iodine was detected only in melanosomes, confirming the specific affinity of the drug for melanin. No drug was found in normal lung tissue.This study demonstrates the potential of SIMS microscopy, which allows the study of ultra structural distribution of a drug within a cell. On the basis of our observations, drug internalization via membrane sigma receptors can be excluded.Progress in cellular imaging allows access not only to qualitative aspects of living structures but also to quantitative data. These data are of considerable interest, especially in pharmaco-toxicology, to understand the mechanisms by which drugs interact with physiological processes. Such analytical methods have, for a long time, been restricted to fluorescence measurements, either directly or after immuno-conjugation, thus severely limiting the development of such applications. In the last few decades, new techniques have appeared, including X-ray fluorescence, electron energy loss spectroscopy, and secondary ion mass spectroscopy (SIMS).Initially introduced 40 years ago [1], SIMS imaging has found its main u