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Reduced Toxicity Following PLDR TBI in a Mouse Model

D Cvetkovic*, B Wang , L Chen , C Ma , Fox Chase Cancer Center, Philadelphia, PA


(Sunday, 7/29/2018) 3:00 PM - 6:00 PM

Room: Exhibit Hall

Purpose: This work compares the effects of conventional radiotherapy (CRT) and pulsed low-dose rate (PLDR) radiation on normal mouse organs in chronic, subacute and acute settings using histopathology.

Methods: A total of 72 nude male mice in three different experimental protocols were randomized into control, CRT and PLDR groups. Experimental settings differed in total body irradiation (TBI) dose and animal survival time following treatment. In a chronic experiment, three fractions of 6 Gy were given 20 days apart, either continuously at a dose rate of 300 MU/min or in 30 pulses of 0.2 Gy with 3 minute intervals, and mice were sacrificed two weeks after the third fraction. In a subacute experiment, mice were exposed to 8 Gy of CRT or PLDR and sacrificed by day 12; the same dose was used in an acute experiment with sacrifice by day three. Animal health and body weight were monitored. At the time of sacrifice brain, heart, lung, liver, spleen, pancreas, gastrointestinal, urinary, reproductive organs, and sternal bone marrow were removed and prepared for histopathologic analysis.

Results: Irrespective of the length of time elapsed from treatment to animal death/sacrifice, equivalent physical doses of CRT triggered significantly more toxicity - cellular atrophy - in normal mouse organs when compared with PLDR, as indicated by hematoxylin and eosin (H&E) staining. The most striking difference in the effect of CRT and PLDR was observed in the bone marrow, spleen and intestine. The degree of atrophy was mild to moderate in PLDR groups, but severe in CRT groups.

Conclusion: Our in vivo findings of reduced toxicity of PLDR in animal tissues support the clinical application of this treatment technique for management of cancer, either for reirradiation or the use of higher tolerable doses in newly diagnosed cases.


Radiation Effects, TBI


TH- Small Animal RT: General (most aspects)

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