Usefulness of positron emission tomographic visualization for examination of in vivo susceptibility to metastasis.
BACKGROUND
Immune surveillance may play a role in protecting against the establishment of metastasis. The authors previously observed that the injection of as few as 10(4) lung metastatic B16BL6 melanoma cells/0.2 mL resulted in no metastasis and in a reduced rate of cell accumulation in the lung, the target organ. In the current study, the authors examined the correlation between metastatic potential and tumor cell trafficking by using a liver-metastatic model.


METHODS
The liver-metastatic potential of RAW117-H10 cells was examined by varying the number of cells injected into mice through the portal vein. To investigate the trafficking of the cells, the authors performed positron emission tomography (PET) analysis, because advances in this technology now enable the use of PET to investigate the real-time trafficking of as few as 10(4) cells/0.2 mL. Furthermore, to clarify the role of the immune defense system, metastatic potential and cell trafficking also were examined by using macrophage-depleted mice.


RESULTS
When 10(6) or 10(5) RAW117-H10 cells/0.2 mL were injected into mice, both quantities of cells caused liver metastasis, cells accumulated in the liver at a similar rate, and there was an approximately 10-fold difference in the number of accumulated cells between the two doses. However, the injection of 10(4) cells/0.2 mL did not produce metastasis, and the accumulation rate in the liver was less than one-tenth of that after the injection of 10(5) cells/0.2 mL. The treatment of mice with 2-chloroadenosine for depleting macrophages prior to the injection of 10(4) cells/0.2 mL resulted in the suppression of the fast elimination of the cells from the liver. Corresponding to this change in PET images, the injection of 10(4) cells/0.2 mL into 2-chloroadenosine-pretreated mice resulted in metastasis.


CONCLUSIONS
The current study suggests that immune surveillance suppresses accumulation of tumor cells to the target and suppresses metastasis, and this effect is obvious when small numbers of tumor cells are used for the challenge. Furthermore, the immune defense system plays a role in the early stage of the metastatic process.
Kikkawa
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H
Department of Radiobiochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
Tsukada
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H
Oku
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N
D000818:Animals; D005260:Female; D007107:Immune System / Q000502:physiology; D008113:Liver Neoplasms / Q000276:immunology / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental; D009360:Neoplastic Cells, Circulating; D014055:Tomography, Emission-Computed; D014407:Tumor Cells, Cultured