Low-dose-rate irradiation by 131I versus high-dose-rate external-beam irradiation in the rat pancreatic tumor cell line CA20948.
OBJECTIVE
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 (131)I.


METHODS
Survival of CA20948 cells was investigated using a clonogenic survival assay after RT by incubation with increasing amounts of (131)I, 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 (alpha/beta) 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.
Department of Nuclear Medicine, Erasmus MC, University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. suzanneverwijnen@hotmail.com
Suzanne
S
Verwijnen
Astrid
A
Capello
Bert
B
Bernard
Gerard
G
van den Aardweg
Mark
M
Konijnenberg
Wout
W
Breeman
Eric
E
Krenning
Marion
M
de Jong
D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects*; D007457:Iodine Radioisotopes / Q000378:metabolism / Q000627:therapeutic use*; D009010:Monte Carlo Method; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D051381:Rats
D007457:Iodine Radioisotopes