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@ARTICLE{Saager:157104,
author = {M. Saager$^*$ and E. W. Hahn and P. Peschke$^*$ and S.
Brons and P. E. Huber$^*$ and J. Debus$^*$ and C.
Karger$^*$},
title = {{R}amipril reduces incidence and prolongates latency time
of radiation-induced rat myelopathy after photon and carbon
ion irradiation.},
journal = {Journal of radiation research},
volume = {61},
number = {5},
issn = {1349-9157},
address = {[Oxford]},
publisher = {Oxford University Press},
reportid = {DKFZ-2020-01395},
pages = {791-798},
year = {2020},
note = {2020 Sep 8;61(5):791-798#EA:E040#LA:E040#},
abstract = {To test the hypothesis that the use of an
angiotensin-converting enzyme inhibitor (ACEi) during
radiotherapy may be ameliorative for treatment-related
normal tissue damage, a pilot study was conducted with the
clinically approved (ACE) inhibitor ramipril on the outcome
of radiation-induced myelopathy in the rat cervical spinal
cord model. Female Sprague Dawley rats were irradiated with
single doses of either carbon ions (LET 45 keV/μm) at the
center of a 6 cm spread-out Bragg peak (SOBP) or 6 MeV
photons. The rats were randomly distributed into 4
experimental arms: (i) photons; (ii) photons + ramipril;
(iii) carbon ions and (iv) carbon ions + ramipril. Ramipril
administration (2 mg/kg/day) started directly after
irradiation and was maintained during the entire follow-up.
Complete dose-response curves were generated for the
biological endpoint radiation-induced myelopathy (paresis
grade II) within an observation time of 300 days.
Administration of ramipril reduced the rate of paralysis at
high dose levels for photons and for the first time a
similar finding for high-LET particles was demonstrated,
which indicates that the effect of ramipril is independent
from radiation quality. The reduced rate of myelopathy is
accompanied by a general prolongation of latency time for
photons and for carbon ions. Although the already clinical
approved drug ramipril can be considered as a mitigator of
radiation-induced normal tissue toxicity in the central
nervous system, further examinations of the underlying
pathological mechanisms leading to radiation-induced
myelopathy are necessary to increase and sustain its
mitigative effectiveness.},
cin = {E040 / E050 / E055},
ddc = {610},
cid = {I:(DE-He78)E040-20160331 / I:(DE-He78)E050-20160331 /
I:(DE-He78)E055-20160331},
pnm = {315 - Imaging and radiooncology (POF3-315)},
pid = {G:(DE-HGF)POF3-315},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32657322},
doi = {10.1093/jrr/rraa042},
url = {https://inrepo02.dkfz.de/record/157104},
}