Ultra-structural cell distribution of the melanoma marker iodobenzamide: improved potentiality of SIMS imaging in life sciences.
BACKGROUND
Analytical imaging by secondary ion mass spectrometry (SIMS) provides images representative of the distribution of a specific ion within a sample surface. For the last fifteen years, concerted collaborative research to design a new ion microprobe with high technical standards in both mass and lateral resolution as well as in sensitivity has led to the CAMECA NanoSims 50, recently introduced onto the market. This instrument has decisive capabilities, which allow biological applications of SIMS microscopy at a level previously inaccessible. Its potential is illustrated here by the demonstration of the specific affinity of a melanoma marker for melanin. This finding is of great importance for the diagnosis and/or treatment of malignant melanoma, a tumour whose worldwide incidence is continuously growing.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Guerquin-Kern
Jean-Luc
JL
INSERM U-350, laboratoire Raymond Latarjet, Bâtiment 112, Centre Universitaire, 91405 Orsay, France. jean-luc.guerquin-kern@curie.u-psud.fr
Hillion
François
F
Madelmont
Jean-Claude
JC
Labarre
Pierre
P
Papon
Janine
J
Croisy
Alain
A
D000818:Animals; D001549:Benzamides / Q000032:analysis* / Q000493:pharmacokinetics; D002451:Cell Compartmentation; D008175:Lung Neoplasms / Q000737:chemistry / Q000556:secondary* / Q000648:ultrastructure; D008543:Melanins / Q000032:analysis*; D008546:Melanoma, Experimental / Q000737:chemistry / Q000556:secondary* / Q000648:ultrastructure; D020460:Melanosomes / Q000737:chemistry / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009368:Neoplasm Transplantation; D018629:Spectrometry, Mass, Secondary Ion / Q000379:methods*
D001549:Benzamides; D008543:Melanins; C066918:N-(2-(diethylamino)ethyl)-4-iodobenzamide