The purpose of this study was to identify the most effective dose and mode of administration of cisplatin for the treatment of malignant brain tumors, using ^<195m>Pt-CDDP.In the present study, we compared the difference of concentrations of cisplatin in tumor tissue, normal brain tissue, and blood between the intracarotid injection group and intravenous injection one for the rat transplanted brain tumors. The dose dependency of each injection method was also analyzed. For each method, the distribution of ^<195m>Pt-radioactivities in DNA,RNA,and protein fractions of the tumor cells were measured by using the fraction method of Schneider with a minor modification.
Intracarotid injections of 1.0mg, 0.5mg, or 0.25mg ^<195m>Pt-CDDP to rats transplanted with C6 glioma were performed. After injection, the tumor tissue, the normal brain tissue, and the blood were sampled for the measurement of Pt uptake. 1) The ratio of Pt uptake of the tumor to that of the blood (T/B), and 2) The ratio of Pt
uptake of the normal brain to that of the blood (N/B) were calculated. 3) The percentages of the amount of ^<195m>Pt uptake in the DNA fraction of tumor cells were also calculated.
Twenty minutes after intracarotid injection of 1.0mg of cisplatin, the results were as follows ; 1) 2.59,2) 0.51,3) 3.65%, 0.5mg ; 1) 1.12,2) 0.10,3) 3.71%, 0.25mg ; 1) 1.06,2) 0.08,3) 3.47%. Sixty minutes after intracarotid injection of 1.0mg of cisplatin, the results were as follows ; 1) 2.79,2) 0.75,3) 3.15%, 0.5mg ; 1) 1.55,2) 0.13,3) 3.86%, 0.25mg ; 1) 1.20,2) 0.10,3) 4.11%. For intravenous injection group, injection of 1.0mg resulted as follows ; 1) 1.41,2) 0.04,3) 3.69%, 0.5mg ; 1) 0.86,2) 0.05,3) 4.23%, 0.25mg ; 1) 0.56,2) 0.07,3) 3.88%. With both intracarotid injection and intravenous injection, the T/B ratio showed a tendency to increase with increase of dosage. The T/B ratios were five times or more higher than the N/B ratios. The T/B ratios were several times higher following intracarotid injection than following intravenous injection. The percentages of the amount of ^<195m>Pt in the DNA fraction of tumor cells was almost the same in each dosage and mode of injection. So, intracarotid injection was superior to intravenous injection in terms of producing a higher dose delivery of cisplatin to the tumor tissue. And the higher the dose, the higher delivery to the tumor tissue. However, further study including the number of the experiments and in vitro experiments are mandatory to obtain a defininte conclusion. Less