The mechanism of 67Ga uptake in animal and human tumours.

The subcellular distribution of 67Ga has been studied by differential centrifugation in 3 transplantable mouse tumours, 3 transplantable rat tumours, 1 dog tumour, 3 human tumour xenografts and 2 human tumours in situ at various times after injection of the citrate complex. From 24 h post injection of nuclide was located predominantly in lysosomal structures in all the tumours studied. Studies in two murine tumours showed marked differences in the rate of lysosomal accumulation of 67Ga. In the ADJ/PC6 plasmacytoma lysosomal uptake of 67Ga had reached a plateau within 15 min while in the S180 tumour lysosomal accumulation of the nuclide occurred over the first 24 h. Normal mouse liver showed a similar pattern to this latter tumour. It is postulated that these variations in the rate of lysosomal accumulation of 67Ga reflect differences in the permeability of the lysosomal membrane. While large amounts of 67Ga were found in the crude nuclear fraction of some tumours this was attributed to unbroken cells as studies with purified nuclei from 7 different tumours indicated that between 2 and 14% of the total tumour 67Ga was associated with the nuclei.