Lysosomal accumulation of 67Ga-transferrin in malignant tumors in relation to their growth rate

Abstract

The binding of 67 Gallium to serum and transferrin was investigated by Sephadex G 50 gel filtration and cellulose acetate electrophoresis combined with autoradiography. The uptake of 67Ga -labelled transferrin in the Morris hepatoma 5123 C, the Novikoff hepatoma and the Yoshida hepatoma AH 130 was studied. A direct correlation between 67Ga -transferrin incorporation and growth rate of the tumors was evident. Increased 67Ga -transferrin accumulation in the tumors of higher proliferation rate was demonstrated qualitatively by tumor scintigraphy as well as quantitatively by measuring the 67Ga -transferrin activity per mg of wet wt tissue. The intracellular localization of the incorporated 67Ga -transferrin was investigated by isolation of subcellular fractions using differential centrifugation. Fractions were identified enzymatically. The maximum 67Ga -transferrin activity was found within the lysosomes of the Morris hepatoma 5123 C, the Novikoff hepatoma, and the Yoshida hepatoma AH 130 very similar to the accumulation within the lysosomes of the hepatic cell. Disappearance of 67Ga -labelled transferrin from the blood was investigated in tumor bearing rats. The blood disappearance rate of 67Ga -transferrin showed a direct correlation to the proliferation rates of the tumors. Furthermore, a close correlation between blood disappearance of 67Ga -transferrin and the mass of tumor cells was evident. The findings indicate the uptake of transferrin into the tumor cell by a process of endocytosis very similar to that found in the normal liver cell. The endocytotic incorporation of transferrin correlates to the proliferation rate of the tumors.