Biological mechanisms of gallium-67 tumor deposition

This investigation was undertaken in order to clarify the tumor deposition mechanisms of 67Ga citrate, a ''universal tumor labeler''. An interspecies comparison of various tumors in the rat and mouse indicated that its highest deposition was in the undifferentiated cell type. Amongst the siblings of experimental tumors, cellular membrane negative charge is greater in the free-cell types than the island-formers: a short-term labeling study revealed a greater 67Ga deposition in the free-cell types. A subcellar fractionation showed an initial association of 67Ga with the nuclear and membrane fractions, and a later transition to the lysosomal. Hypotonic lysis revealed a paralleled release of 67Ga and lysosomal key enzymes. Morphological abnormality of the cancer lysosomes was thought to agree with their Ga retention. This property was clinically confirmed by a scintiscoring technique. Treatment with cold gallium of tumors modified the biological parameters of tumor growth: in vitro it suppressed cell proliferation, reduced saturation density; and produced cellular pleomorphism. In vivo it increased tumor consistency by reducing central necrosis and increasing the viable cell layer thickness. Thus, 67Ga deposition is closely related to various biological parameters of malignancy including the cellular membrane negative charge as cancer is a membrane disorder, and the lysosomal morphology and function. (author)