LABORATORY STUDIES AND CLINICAL TRIALS OF CHEMICAL RADIO-SENSITIZERS 



to the dimensions of the aperture is of great importance in order to avoid the 

 'edge miss'. The dose-rate was measured in a wax phantom by Miss R. 

 Saunders, who has kindly suppHed the following information. The phantom 

 made of wax of density 0-90g per c.c. is shaped to represent a tumour 



4 X 3 cm and 2 -6 cm high on a base of dimensions representing a 200 g 

 rat. A hole was made to accommodate a 250 r Victoreen chamber hori- 

 zontally along a 3 cm axis the external diameter of the chamber being 

 0-9 cm and the centre of the chamber 1 cm from the upper surface of the 

 phantom. The wax phantom was wrapped in a lead sheet through which 

 the 'tumour' projected. The end of the chamber was supported by a bolus 

 bag. The Maximar X-ray machine was run at 220 kV and an added filter 

 of 1 mm aluminium was used (H.V.L. = 0-4 mm copper ; effective wave- 

 length 0-25 A). The chamber was exposed for 1 minute. The end of the 



5 cm circular applicator just touched the top of the phantom. The F.S.D. 

 of the applicator was 41 •5 cm. The Victoreen readings were corrected for 

 wavelength, temperature and pressure. The dose-rate at the centre of the 

 tumour was in the region of 160 r per minute, but the exact value as measured 

 was used in each experiment. 



While permanent retrogression of the tumour is the main criterion studied, 

 measurements of the tumour dimensions and the weight of the rats have 

 been recorded three times weekly before and indefinitely after irradiation 

 in all these experiments. Many histological examinations have been made 

 to confirm the presence of tumour and the effects of radiation and chemicals 

 on the tumour and on normal tissues. It is to be noted that throughout 

 these experiments the animals have all been treated as individuals. I wish 

 to express my thanks to Mr. E. A. King for his skilled help in these 

 experiments. 



The results of the experiments with the Walker rat carcinoma 256, in 

 Tables I and // show that Compound I, when administered by the intra- 

 venous route at 30 minutes before a single therapeutic dose of X-radiation, 

 produces definite radio-sensitization as estimated by a significant increase 

 in the proportion of primary tumours showing permanent retrogression. 

 The administration of Compound I by intramuscular injection ( Table II) 

 shows that the intramuscular route is completely ineffective except possibly 

 when given in very large doses over very prolonged periods. In doses com- 

 parable with those used clinically, intramuscular administration has no 

 effect as a radio-sensitizer and no significant effect on the tumour. The 

 ineffectiveness of the intramuscular route serves as a control for the experi- 

 ments with intravenous administration. The experiments with intra- 

 muscular injection of Compound I were carried out before the technique of 

 transplantation of the tumour was fully developed. It can be seen from the 

 experiments in the intravenous series that for radio-sensitization with Com- 

 pound I the best results are obtained when the intravenous injection is made 

 at about 30 minutes before the beginning of the X-ray exposure. 



The results of the similar experiment with Compound XXVIII, reported 

 elsewhere (Mitchell^), are given in more detail in Table II. Again, 

 the ineffectiveness of the intramuscular route serves as a control. The 

 experiments with intravenous administration include a number with unsuit- 

 able timing. With Compound XXVIII by intravenous injection it appears 



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