Tissue distribution and retention of 5-thio-D-glucose in animal tumor models.
5-Thio-D-glucose (5-TDG) has demonstrated potential as a radiation sensitizer for hypoxic cells growing in monolayer culture and as multicell spheroids. We have studied the biodistribution and pharmacokinetics of radiolabeled (35S or 3H) 5-TDG prior to utilizing this bioisotere of D-glucose for radiation sensitization studies in vivo. At all times after administration, 5-TDG achieved higher tissue levels of radioactivity in hamster pancreatic tumors of ductal and acinar cell origin than in the normal pancreas. By 2 hours after intravenous injection, the duct tumor activity concentration exceeded that of any other tissue; a similar situation obtained after 4 hours in the acinar tumor model. However, the functioning insulinoma model exhibited similar radioactivity uptake and kinetics as did normal pancreas. In all models, metastases behaved similarly to the primary transplanted tumor in terms of uptake and retention of radioactivity. Addition of carrier 5-TDG appeared to abrogate much of the selective uptake of label into tumor relative to normal tissue, in terms of % dose/g tissue, but the total uptake into tumor was greater. The drug is rapidly excreted in the urine and the nature of this excretion was examined. Retention of activity in normal lung tissue was similar to that of pancreatic tumors and prompted a study of uptake into Lewis lung carcinoma. Again, tumor uptake in % dose/g approximated uptake into normal lung tissue, but total uptake into tumor was greater. These studies provided the basis for initiation of in vivo studies of potential cytotoxic and radiation-potentiating activity of 5-TDG.[1]References
- Tissue distribution and retention of 5-thio-D-glucose in animal tumor models. Markoe, A.M., Risch, V.R., Emrich, J., Fala, S., Brady, L.W. Cancer clinical trials. (1980) [Pubmed]
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