Page 212 - 2014 Printable Abstract Book
P. 212
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(PS3-39) Effects of radiation on sunitinib toxicity in the heart. Vijayalakshmi Sridharan, PhD ; Preeti
2
1
1
1
Tripathi, MS ; Sunil Sharma, PhD ; Eduardo G. Moros, PhD ; Martin Hauer-Jensen, MD, PhD ; and Marjan
1
1
Boerma, PhD , University of Arkansas for Medical Sciences, Little Rock, AR and Moffitt Cancer Center,
Tampa, FL
2
Background: Radiation-induced heart disease is a potentially severe side effect of radiotherapy of
the thoracic region. Sunitinib, a tyrosine kinase inhibitor and anticancer agent, is also known to produce
cardiac dysfunction. Although sunitinib is often used simultaneously with radiotherapy to treat cancers of
the thoracic region, mechanisms by which radiation interacts with the toxic effects of sunitinib are
unknown. To test whether radiation can alter the cardiotoxicity of sunitinib, the present study investigates
the effects of local heart irradiation and sunitinib in the rat heart. Methods: Male Sprague-Dawley rats
received localized image-guided irradiation to the heart at a dose of 21 Gy or a fractionated dose of 9 Gy
for 5 days. Starting from the first day of irradiation, rats were orally administered 8mg/kg body weight
sunitinib or vehicle, every day for two weeks. At 2 weeks after irradiation, apoptosis and autophagy were
assessed. Because sunitinib was previously shown to cause cardiac toxicity in animal models via inhibition
of pericytes, levels of pericyte marker NG-2 were studied by immunoblotting. Mitochondria were
examined for opening of the membrane permeability transition pore (mPTP) by using a mitochondrial
swelling assay. Results: Both single dose and fractionated irradiation did not modify the levels of total Bax
and Bcl2 in sunitinib treated rats, but they caused a small but significant increase in the number of
apoptotic cells. Local heart irradiation in combination with sunitinib treatment did not significantly modify
markers of autophagy and or alter the pericyte marker NG2. Calcium-induced mitochondrial swelling was
enhanced in the combined treatment group when compared to sunitinib or radiation alone. Conclusions:
When combined with sunitinib, both single dose and fractionated irradiation caused moderate increases
in apoptosis and mitochondrial swelling in the heart.
(PS3-40) Measurement of the stopping power of liquid water for carbon ions in the energy range
2
1; 2
1
1
between 1 MeV and 5 MeV. Johannes M. Rahm ; Woon Yong Baek ; Hans Rabus ; and Hans Hofsäss
1
Physikalisch-Technische Bundesanstalt, Braunschweig, Germany and Georg-August Universität,
Göttingen, Germany
2
Cancer therapy with carbon ions has gained increasing interest in the last decade due to its
advantageous dose distributions. For dosimetry and treatment planning the accurate knowledge of the
stopping power of liquid water for carbon ions is the crucial parameter. At high projectile energies,
calculation of the stopping power can be performed by means of the Bethe-Bloch equation. The Bethe-
Bloch equation is only limited valid if the ions have a velocity comparable to the velocity of the valence
electrons of the target. To our knowledge there exist no experimental data for the stopping power of
liquid water for carbon ions in the energy range of their maximum stopping power. This lack of information
motivated this current work. For this measurement the Doppler-shift of the gamma quanta emitted from
excited carbon nuclei which are produced by a 12C (a, a') 12C* reaction is used. The amount of the
Doppler-shift depends on the velocity of the carbon nuclei and the emission angle of the γ-quanta. The
Doppler-shifted γ-energy spectrum is recorded with a high purity germanium detector. This γ-energy
spectrum contains the information of the stopping power of the target. Since the lifetime of the first
excited state of carbon nuclei is known, the stopping power can be determined by comparing the γ-energy
spectrum produced by excited carbon nuclei slowing down in the respective target and vacuum. For the
210 | P a g e
(PS3-39) Effects of radiation on sunitinib toxicity in the heart. Vijayalakshmi Sridharan, PhD ; Preeti
2
1
1
1
Tripathi, MS ; Sunil Sharma, PhD ; Eduardo G. Moros, PhD ; Martin Hauer-Jensen, MD, PhD ; and Marjan
1
1
Boerma, PhD , University of Arkansas for Medical Sciences, Little Rock, AR and Moffitt Cancer Center,
Tampa, FL
2
Background: Radiation-induced heart disease is a potentially severe side effect of radiotherapy of
the thoracic region. Sunitinib, a tyrosine kinase inhibitor and anticancer agent, is also known to produce
cardiac dysfunction. Although sunitinib is often used simultaneously with radiotherapy to treat cancers of
the thoracic region, mechanisms by which radiation interacts with the toxic effects of sunitinib are
unknown. To test whether radiation can alter the cardiotoxicity of sunitinib, the present study investigates
the effects of local heart irradiation and sunitinib in the rat heart. Methods: Male Sprague-Dawley rats
received localized image-guided irradiation to the heart at a dose of 21 Gy or a fractionated dose of 9 Gy
for 5 days. Starting from the first day of irradiation, rats were orally administered 8mg/kg body weight
sunitinib or vehicle, every day for two weeks. At 2 weeks after irradiation, apoptosis and autophagy were
assessed. Because sunitinib was previously shown to cause cardiac toxicity in animal models via inhibition
of pericytes, levels of pericyte marker NG-2 were studied by immunoblotting. Mitochondria were
examined for opening of the membrane permeability transition pore (mPTP) by using a mitochondrial
swelling assay. Results: Both single dose and fractionated irradiation did not modify the levels of total Bax
and Bcl2 in sunitinib treated rats, but they caused a small but significant increase in the number of
apoptotic cells. Local heart irradiation in combination with sunitinib treatment did not significantly modify
markers of autophagy and or alter the pericyte marker NG2. Calcium-induced mitochondrial swelling was
enhanced in the combined treatment group when compared to sunitinib or radiation alone. Conclusions:
When combined with sunitinib, both single dose and fractionated irradiation caused moderate increases
in apoptosis and mitochondrial swelling in the heart.
(PS3-40) Measurement of the stopping power of liquid water for carbon ions in the energy range
2
1; 2
1
1
between 1 MeV and 5 MeV. Johannes M. Rahm ; Woon Yong Baek ; Hans Rabus ; and Hans Hofsäss
1
Physikalisch-Technische Bundesanstalt, Braunschweig, Germany and Georg-August Universität,
Göttingen, Germany
2
Cancer therapy with carbon ions has gained increasing interest in the last decade due to its
advantageous dose distributions. For dosimetry and treatment planning the accurate knowledge of the
stopping power of liquid water for carbon ions is the crucial parameter. At high projectile energies,
calculation of the stopping power can be performed by means of the Bethe-Bloch equation. The Bethe-
Bloch equation is only limited valid if the ions have a velocity comparable to the velocity of the valence
electrons of the target. To our knowledge there exist no experimental data for the stopping power of
liquid water for carbon ions in the energy range of their maximum stopping power. This lack of information
motivated this current work. For this measurement the Doppler-shift of the gamma quanta emitted from
excited carbon nuclei which are produced by a 12C (a, a') 12C* reaction is used. The amount of the
Doppler-shift depends on the velocity of the carbon nuclei and the emission angle of the γ-quanta. The
Doppler-shifted γ-energy spectrum is recorded with a high purity germanium detector. This γ-energy
spectrum contains the information of the stopping power of the target. Since the lifetime of the first
excited state of carbon nuclei is known, the stopping power can be determined by comparing the γ-energy
spectrum produced by excited carbon nuclei slowing down in the respective target and vacuum. For the
210 | P a g e
