Page 232 - 2014 Printable Abstract Book
P. 232
chemoradiotherapy. Fluorothymidine (FLT) and 5-Fluorouracil (5FU) chemotherapeutic drugs are
radiosensitizers which able to bind to tumoral DNA and inhibit the DNA damage repair after ionizing
radiation. Radiotherapy by targeted radionuclide is another approach allowing the localization of the
radiation mainly in tumor tissues and therefore protecting the surrounding healthy tissues. The purpose
18
of this study was to evaluate the efficiency of the F radionuclide incorporated in two well know
18
18
18
chemotherapeutic drugs being consequently F-FLT and F-5FU. The F radionuclide emits positron with
the range of energy proper for radiotherapy whereas the molecules properties are already known to
target the tumor cells. These radioactive drugs were administered intratumoral (i.t.) into subcutaneous
colorectal tumors (HCT116 cell line) implanted in an immunosuppressed nu/nu nude mice. The kinetic of
18
18 F-FLT and F-5FU was determined by PET imaging with the dose of 1 MBq from 30 minutes to 2 hours
18
18
after drug injection. The chemoradiation responses of F-FLT and F-5FU with a dose of 3.5 and 25 MBq
were evaluated and compared with the non-radioactive FLT and 5FU. The treatment efficacy was
determined by comparing the tumor growth delay of each group. Our results showed the localization of
radioactive drug at the site of i.t. injection. The tumoral accumulation of radioactive drugs was gradually
decreased with time after injection. The tumors treated with radioactive drugs showed significant tumor
growth delays compared to the untreated tumors or the tumors treated with the non-radioactive drugs.
18
18
This study showed that F-FLT and F-5FU permit to do tumor targeted chemoradiotherapy while
allowing PET imaging of these radioactive drugs in the tumor and all other organs. This enhancement
could be used in the future to improve local control with chemoradiation treatment for colorectal cancer.
(PS3-78) A rat MR imaging model to study radiation induced bone marrow damage and recovery. Solmaz
2
1
2
1
2
F. Afshar ; M. Waleed. Gaber ; Aurash A. Bina ; Caterina C. Kaffes ; and Omaima M. Sabek
1
2
Houston Methodist Hospital, Houston, TX and Baylor College of Medicine, Houston, TX
Bone marrow damage, a hallmark of the hematopoietic syndrome, is one of the main effects of
radiation exposure. There are three characteristics of radiation damage to the bone marrow: vascular
damage, loss of hematopoietic progenitors, and fat formation. Imaging of irradiation damage would be
beneficial in triaging and diagnosing the degree of damage, as well as tracking bone marrow recovery.
Magnetic resonance imaging (MRI) can be used to study fat formation using a T1 measurement, and the
severity of vascular damage using ultrasmall superparamagnetic iron oxide (USPIO) particles in a T2
weighted scan. Although MR imaging does not track progenitor loss, nevertheless we show that it is
associated with fat formation in the T1 weighted image. Sprague-Dawley rats age 5-6 weeks were
irradiated using an x-ray source (RS2000, 160 kVp) at a dose rate of 116 cGy/min. The animal was given a
radiation dose of 7.5Gy, its right leg shielded using a lead piece 2 cm thick. When using the T2 weighted
MR scan, rats were injected with USPIO particles intravenously and imaged pre and post injection. The
loss of hematopoietic progenitors was visualized using histopathology. Hemorrhaging of the vasculature
is evident by a significant difference (p=0.0485) in the ∆R2 value of the irradiated leg versus the shielded
leg two days post partial body irradiation. The T1 weighted scan showed an increase in fat formation in
the irradiated leg, significantly higher than that of the shielded leg (p <0.0001 at day 5 and day 10, no
significance at day 2), and increased significantly over time (p <0.0001). Using hematoxylin and eosin
staining (H&E) of paraffin embedded sections, we observed a decrease in progenitors in the irradiated left
leg compared to the shielded right leg at 2 days post irradiation. By day 10, the density of progenitors in
the bone marrow of the irradiated leg recovered to a level similar to control. We have shown that MR
imaging is a tool that can be used to diagnose and follow bone marrow damage and recovery. We show
230 | P a g e
radiosensitizers which able to bind to tumoral DNA and inhibit the DNA damage repair after ionizing
radiation. Radiotherapy by targeted radionuclide is another approach allowing the localization of the
radiation mainly in tumor tissues and therefore protecting the surrounding healthy tissues. The purpose
18
of this study was to evaluate the efficiency of the F radionuclide incorporated in two well know
18
18
18
chemotherapeutic drugs being consequently F-FLT and F-5FU. The F radionuclide emits positron with
the range of energy proper for radiotherapy whereas the molecules properties are already known to
target the tumor cells. These radioactive drugs were administered intratumoral (i.t.) into subcutaneous
colorectal tumors (HCT116 cell line) implanted in an immunosuppressed nu/nu nude mice. The kinetic of
18
18 F-FLT and F-5FU was determined by PET imaging with the dose of 1 MBq from 30 minutes to 2 hours
18
18
after drug injection. The chemoradiation responses of F-FLT and F-5FU with a dose of 3.5 and 25 MBq
were evaluated and compared with the non-radioactive FLT and 5FU. The treatment efficacy was
determined by comparing the tumor growth delay of each group. Our results showed the localization of
radioactive drug at the site of i.t. injection. The tumoral accumulation of radioactive drugs was gradually
decreased with time after injection. The tumors treated with radioactive drugs showed significant tumor
growth delays compared to the untreated tumors or the tumors treated with the non-radioactive drugs.
18
18
This study showed that F-FLT and F-5FU permit to do tumor targeted chemoradiotherapy while
allowing PET imaging of these radioactive drugs in the tumor and all other organs. This enhancement
could be used in the future to improve local control with chemoradiation treatment for colorectal cancer.
(PS3-78) A rat MR imaging model to study radiation induced bone marrow damage and recovery. Solmaz
2
1
2
1
2
F. Afshar ; M. Waleed. Gaber ; Aurash A. Bina ; Caterina C. Kaffes ; and Omaima M. Sabek
1
2
Houston Methodist Hospital, Houston, TX and Baylor College of Medicine, Houston, TX
Bone marrow damage, a hallmark of the hematopoietic syndrome, is one of the main effects of
radiation exposure. There are three characteristics of radiation damage to the bone marrow: vascular
damage, loss of hematopoietic progenitors, and fat formation. Imaging of irradiation damage would be
beneficial in triaging and diagnosing the degree of damage, as well as tracking bone marrow recovery.
Magnetic resonance imaging (MRI) can be used to study fat formation using a T1 measurement, and the
severity of vascular damage using ultrasmall superparamagnetic iron oxide (USPIO) particles in a T2
weighted scan. Although MR imaging does not track progenitor loss, nevertheless we show that it is
associated with fat formation in the T1 weighted image. Sprague-Dawley rats age 5-6 weeks were
irradiated using an x-ray source (RS2000, 160 kVp) at a dose rate of 116 cGy/min. The animal was given a
radiation dose of 7.5Gy, its right leg shielded using a lead piece 2 cm thick. When using the T2 weighted
MR scan, rats were injected with USPIO particles intravenously and imaged pre and post injection. The
loss of hematopoietic progenitors was visualized using histopathology. Hemorrhaging of the vasculature
is evident by a significant difference (p=0.0485) in the ∆R2 value of the irradiated leg versus the shielded
leg two days post partial body irradiation. The T1 weighted scan showed an increase in fat formation in
the irradiated leg, significantly higher than that of the shielded leg (p <0.0001 at day 5 and day 10, no
significance at day 2), and increased significantly over time (p <0.0001). Using hematoxylin and eosin
staining (H&E) of paraffin embedded sections, we observed a decrease in progenitors in the irradiated left
leg compared to the shielded right leg at 2 days post irradiation. By day 10, the density of progenitors in
the bone marrow of the irradiated leg recovered to a level similar to control. We have shown that MR
imaging is a tool that can be used to diagnose and follow bone marrow damage and recovery. We show
230 | P a g e
