Low-Dose-Rate Irradiation by 131 I Versus High-Dose-Rate External-Beam Irradiation in the Rat Pancreatic Tumor Cell Line CA20948

Abstract

Aim: The rat pancreatic CA20948 tumor cell line is widely used in receptor-targeted preclinical studies because many different peptide receptors are expressed on the cell membrane. The response of the tumor cells to peptide radionuclide therapy, however, is dependent on the cell line's radiosensitivity. Therefore, we measured the radiosensitivity of the CA20948 tumor cells by using clonogenic survival assays after high-energy external-beam radiotherapy (XRT) in vitro. It can, however, be expected that results of high-dose-rate XRT are not representative for those after low-dose-rate radionuclide therapy (RT), such as peptide-receptor radionuclide therapy. Therefore, we compared clonogenic survival in vitro in CA20948 tumor cells after increasing doses of XRT or RT, the latter using ¹³¹I. Methods: Survival of CA20948 cells was investigated using a clonogenic survival assay after RT by incubation with increasing amounts of ¹³¹I, leading to doses of 1–10 Gy after 12 days of incubation (maximum dose rate, 0.92 mGy/min), or with doses of 1–10 Gy using an X-ray machine (dose rate, 0.66 Gy/min). Colonies were scored after a 12-day–incubation period. Also, the doubling time of this cell line was calculated. Results: We observed a dose-dependent reduction in tumor-cell survival, which, at low doses, was similar for XRT and RT. For high-dose-rate XRT, the quadratic over linear component ratio (α/β) for CA20948 was 8.3 Gy, whereas that ratio for low-dose-rate RT was calculated to be 86.5 Gy. The calculated doubling time of CA20948 cells was 22 hours. Conclusions: Despite the huge differences in dose rate, RT tumor cell–killing effects were approximately as effective as those of XRT at doses of 1 and 2 Gy, the latter being the common daily dose given in fractionated external-beam therapies. At higher doses, RT was less effective than XRT.