Intratumoral distribution of tritiated-FDG in breast carcinoma: correlation between Glut-1 expression and FDG uptake

Abstract

Increased expression of glucose transporters is frequently associated with transformation and is often found in malignant tumors. To assess the relationship between cellular glucose transporter Glut-1 (brain/erythrocyte) and FDG uptake in malignant tumors we studied the expression of Glut-1 and 3H-FDG uptake in a syngeneic rat mammary cancer (RMC), an animal tumor model that closely mimics human breast carcinoma.

Methods: Tumors of 1-9 RMT cell line were grown in female Lewis rats and were studied by immunoperoxidase staining with anti-Glut-1 antibodies, macro- and microautoradiography and densitometry following intravenous injection of 3H-FDG.

Results: Most of the cancer cells contained Glut-1 positive cytoplasmic granules. Cells with strongly stained cell membrane were mainly observed in areas of intensive intraductal proliferation and high tumor cell density. No staining was observed in necrotic areas, connective tissue stroma or granulation tissue. FDG uptake in areas of high cancer cell density was consistently higher than average tumor uptake. Silver grain counts were 31 +/- 8/0.023 mm2 in regions of viable cancer cells, and were higher as compared to 10 +/-7 counted in necrotic or 8 +/- 8 in connective tissue areas (p = 0.0001). Densitometry of the autoradiograms and of the histochemically stained consecutive sections showed positive correlation between estimates of FDG uptake and the intensity of staining of the Glut-1 antigen (r=0.3-0.6; p=0.0001).

Conclusion: Our results demonstrate significant positive correlation between the expression of the facilitative glucose transporter Glut-1 and FDG accumulation in viable cancer cells in the syngeneic rat breast cancer. They suggest that the regulation of FDG uptake may be mediated by Glut-1 and the heterogeneous expression of Glut-1 and tracer uptake may reflect localized variations in the metabolic conditions.