Radiation administered as a large single dose or in a fractionated schedule: Role of the tumour vasculature as a target for influencing response

Abstract

This study was designed to demonstrate a differential tumour response to radiation given as a large single dose or fractionated, and to investigate the postulated role of the tumour vasculature as a target for this difference. A C3H mammary carcinoma grown in the right rear foot of female CDF1 mice was used when at 200 mm³. Radiation (240 kV x-rays) was given locally to the tumour bearing foot either as 1×20 Gy or 10×2 Gy (2 fractions/day). Tumour response was assessed by calculating tumour growth time (TGT; time to grow to 3 times treatment volume). Vascular effects were monitored by performing dynamic contrast enhanced-magnetic resonance imaging using a 3-Tesla magnet and the contrast agent gadolinium (Gd)-DTPA. The endpoint was the initial area under the concentration curve (IAUC) following Gd-DTPA. The mean (±1 S.E.) TGT for control mice was 4.0 days (±0.2). This was significantly (Student's t-test; p < 0.05) increased to 12.9 (±0.6) and 19.8 (±0.7) days, by 10×2 and 1×20 Gy, respectively. The mean (±1 S.E.) of the median IAUC values for control tumours was 8.4 mMs (±0.5). This was non-significantly increased to 9.4 mMs (±0.4) 6-hours after 1×20 Gy, but then significantly decreased to a nadir of 6.8 mMs (±0.5) after 48-hours. IAUC recovered at longer time intervals. With 10×2 Gy, IAUC significantly decreased during irradiation, reaching 6.7 (±0.3) and 5.6 (±0.3) mMs at the mid-point and end of the irradiation period, respectively. IAUC recovered 24-hours after irradiating before significantly decreasing to 4.4 mMs (±0.3) at 48-hours. Our results confirm that radiation given in a large single dose is superior to the same dose given in a more conventional fractionated schedule, but vascular-mediated effects did not account for this difference in radiation sensitivity.