Tumor kinetics and timing of the second dose to improve tumor radiocurability--a prediction of the best timing for fractionation by measuring 125I-iododeoxyuridine uptake in situ.

Experimental radiotherapy using two fractions of X-rays was carried out to study the best time of the second dose to improve the radiocurability of squamous cell carcinoma in WHT/Ht strain mice. Second doses of 27 Gy were given at 0, 6, 12, 24, 60 and 100 h after the first irradiation of 10 Gy. Each time interval relates to a specific change in tumor cell kinetics after irradiation of 10 Gy, that is, completion of PLD and SLD repair, most depression of 125I-IUdR uptake, beginning of increase of clonogenic cells, maximum cell loss rate and bottom regrowth curve, for 6, 12, 24, 60 and 100 h respectively. The local tumor control rates were 100, 78.1 and 96.8% for 0, 6 and 12 h respectively, and then control rates gradually decreased as interval times got longer. A second time window of local control was found 12 h after the first irradiation. This time corresponded to minimal uptake of 125I-IUdR, implying a decrease of S stage cells and depressed DNA synthesis, as suggested from labeling index and grain count studies. Twelve hours may be also the time when cells accumulate at the G2 stage (G2 block) or just after release of the G2 block from the kinetic viewpoint. The 125I-IUdR uptake method may be useful in determining the best time interval for fractionation in situ.