Page 351 - 2014 Printable Abstract Book
P. 351
(PS6-45) Characterization of a minipig model of Gastrointestinal Acute Radiation Syndrome using Total
1
Body Irradiation (TBI) and Partial Body Irradiation (PBI). Wieslaw Wierzbicki, PhD ; Martin Hauer-
3
2
3
3
Jensen ; Mylene Pouliot, PhD ; Julius Haruna, DVM, MSc, Dipl. ACVP ; Leanne Bassett, BSc ; Alexis Ascah,
3
1
3
PhD ; and Simon Authier, DVM, MBA, PhD, DSP , Hopital Maisonneuve-Rosemont, Montreal, Canada ;
3
University of Arkansas for Medical Sciences, Little Rock, AR ; and CiToxLAB, Laval, Canada
2
The gastrointestinal (GI) tract of minipigs presents similarities with humans including transit time,
adaptation to an omnivore diet and humidity content of feces which impacts the bacterial flora. The
minipig is a potentially valuable model for GI-ARS treatments. A set-up was designed for total body
irradiation (TBI) and partial body irradiation (PBI) in conscious minipigs. Dosimetry measurements were
made in experimental conditions using a custom-made mini-pig acrylic phantom, a solid water phantom
with Markus and Farmer ionization chambers. Each animal was irradiated with a single dose up to 12 Gy
in 2 lateral fractions, one on each side. For PBI, Cerrobend shielding (9 cm) provided attenuation of the
dose delivered to the pelvic legs with the resulting bone marrow dose under 7 % of the midplane dose
delivered to the body. Nanodots and superflab buildup material were used to validate the treatment dose
and protected bone marrow dose. A minipig acrylic phantom was used to produce adequate dose
scattering conditions. Real-time, in-vivo dosimetry was implemented during animal exposure using a
Farmer chamber subjected to an electrometer bias voltage of -300V confirming accuracy under 2% of
prescribed dose. Emesis up to several days after radiation and partial to complete anorexia were
consistently observed. Bone marrow shielding resulted in an attenuation of radiation induced bone
marrow depletion with higher counts after PBI compared to TBI for all lineages. In decreasing order, the
most important protective effects were noted in lymphocytes, neutrophils, reticulocytes and platelets.
Pathology confirmed minimal to moderate loss/atrophy of intestinal crypts in most GI segments with
villous atrophy (villi height shortening) in the small intestines of up to 70-80% compared to sham
irradiated minipigs. Up to marked intestinal crypt degeneration/regeneration was observed. Erosions and
ulcerations were noted in all GI segments at Day 7 post-exposure. The overall cellularity (lymphocyte,
plasma cell etc.) in the GI lamina propria was decreased with both TBI and PBI. Evidences of bacterial
colonization were noted in the intestines and stomach. Evidence of hemorrhages were noted in several
tissues but were more widespread after TBI suggesting protective effects of bone marrow sparing with
PBI on this sequelea.
(PS6-46) Characterization of murine model of radiation induced pulmonary injury using partial body
1
1
2
irradiation. Simon Authier, DVM, MBA, PhD, DSP ; Mylene Pouliot, PhD ; Lynn Maine, PhD ; Wieslaw
1
1
3
Wierzbicki, PhD ; and Alexis Ascah, PhD , CiToxLAB, Laval, Canada ; Apogee Biotechnology Corporation,
3
2
Hummelstown, PA ; and Hopital Maisonneuve-Rosemont, Montreal, Canada
Introduction: Delayed radiation-induced damage to the lungs is a primary cause of mortality after
recovery from an acute radiation syndrome. In addition to the acute effects of radiation exposure,
development of medical countermeasures may focus on protection against late radiation-induced
injuries. Current regulations require evaluation of radiomitigation drug candidate efficacy in a rodent and
a non-rodent model for approval under the FDA Animal Rule. In this study, a murine model of partial body
irradiation was characterized assessing long-term survival and pulmonary changes following irradiation.
Methods: A total of 270 male C57BL/6 mice were exposed to whole-body irradiation (Cobalt-60) at a dose
level of 15.25 or 16 Gy and a dose rate of 60 cGy/min, with the left pelvic limb shielded with a cerrobend
349 | P a g e
1
Body Irradiation (TBI) and Partial Body Irradiation (PBI). Wieslaw Wierzbicki, PhD ; Martin Hauer-
3
2
3
3
Jensen ; Mylene Pouliot, PhD ; Julius Haruna, DVM, MSc, Dipl. ACVP ; Leanne Bassett, BSc ; Alexis Ascah,
3
1
3
PhD ; and Simon Authier, DVM, MBA, PhD, DSP , Hopital Maisonneuve-Rosemont, Montreal, Canada ;
3
University of Arkansas for Medical Sciences, Little Rock, AR ; and CiToxLAB, Laval, Canada
2
The gastrointestinal (GI) tract of minipigs presents similarities with humans including transit time,
adaptation to an omnivore diet and humidity content of feces which impacts the bacterial flora. The
minipig is a potentially valuable model for GI-ARS treatments. A set-up was designed for total body
irradiation (TBI) and partial body irradiation (PBI) in conscious minipigs. Dosimetry measurements were
made in experimental conditions using a custom-made mini-pig acrylic phantom, a solid water phantom
with Markus and Farmer ionization chambers. Each animal was irradiated with a single dose up to 12 Gy
in 2 lateral fractions, one on each side. For PBI, Cerrobend shielding (9 cm) provided attenuation of the
dose delivered to the pelvic legs with the resulting bone marrow dose under 7 % of the midplane dose
delivered to the body. Nanodots and superflab buildup material were used to validate the treatment dose
and protected bone marrow dose. A minipig acrylic phantom was used to produce adequate dose
scattering conditions. Real-time, in-vivo dosimetry was implemented during animal exposure using a
Farmer chamber subjected to an electrometer bias voltage of -300V confirming accuracy under 2% of
prescribed dose. Emesis up to several days after radiation and partial to complete anorexia were
consistently observed. Bone marrow shielding resulted in an attenuation of radiation induced bone
marrow depletion with higher counts after PBI compared to TBI for all lineages. In decreasing order, the
most important protective effects were noted in lymphocytes, neutrophils, reticulocytes and platelets.
Pathology confirmed minimal to moderate loss/atrophy of intestinal crypts in most GI segments with
villous atrophy (villi height shortening) in the small intestines of up to 70-80% compared to sham
irradiated minipigs. Up to marked intestinal crypt degeneration/regeneration was observed. Erosions and
ulcerations were noted in all GI segments at Day 7 post-exposure. The overall cellularity (lymphocyte,
plasma cell etc.) in the GI lamina propria was decreased with both TBI and PBI. Evidences of bacterial
colonization were noted in the intestines and stomach. Evidence of hemorrhages were noted in several
tissues but were more widespread after TBI suggesting protective effects of bone marrow sparing with
PBI on this sequelea.
(PS6-46) Characterization of murine model of radiation induced pulmonary injury using partial body
1
1
2
irradiation. Simon Authier, DVM, MBA, PhD, DSP ; Mylene Pouliot, PhD ; Lynn Maine, PhD ; Wieslaw
1
1
3
Wierzbicki, PhD ; and Alexis Ascah, PhD , CiToxLAB, Laval, Canada ; Apogee Biotechnology Corporation,
3
2
Hummelstown, PA ; and Hopital Maisonneuve-Rosemont, Montreal, Canada
Introduction: Delayed radiation-induced damage to the lungs is a primary cause of mortality after
recovery from an acute radiation syndrome. In addition to the acute effects of radiation exposure,
development of medical countermeasures may focus on protection against late radiation-induced
injuries. Current regulations require evaluation of radiomitigation drug candidate efficacy in a rodent and
a non-rodent model for approval under the FDA Animal Rule. In this study, a murine model of partial body
irradiation was characterized assessing long-term survival and pulmonary changes following irradiation.
Methods: A total of 270 male C57BL/6 mice were exposed to whole-body irradiation (Cobalt-60) at a dose
level of 15.25 or 16 Gy and a dose rate of 60 cGy/min, with the left pelvic limb shielded with a cerrobend
349 | P a g e
