WE‐E‐108‐08: Dosimetric and Biological Benchmarking of a Murine Total Marrow Irradiation Platform

R. Azimi, P. Alaei, Y. Takahashi, E. Spezi, M. Yagi, L. Arentsen, L. Sharkey, D. Seelig, J. Schappa, S. Hui

Research output: Contribution to journalArticle

Abstract

Purpose: Increased radiation dose for recently developed clinical total marrow irradiation (TMI) facilitates bone marrow transplants for high risk leukemia patients but its mechanism and role is completely unknown. To initiate this high impact, clinically relevant, investigation, a murine TMI‐like system has been developed and benchmarked. Detailed dosimetric characterization of the irradiator, toxicity to critical organs, and molecular imaging biomarkers were evaluated. Methods: An orthovoltage x‐ray unit was commissioned and calibrated following TG‐61 protocol. A special irradiation jig utilizing compensators has been developed to reduce the dose to eyes, brain, lungs, heart, and gastrointestinal tract. Validation of the dosimetry has been performed using TLDs, Gafchromic film, ionization chamber, and Monte Carlo calculations. Mice were irradiated for TBI and TMI. Live and longitudinal pre and post radiation (day 2) FDG microPET/CT imaging was performed. Certain organs such as lungs, liver, kidney, gut and brain were harvested post radiation for the purpose of cellular and histological studies using thymidine analog 5‐bromo‐2‐deoxyuridine (BrdU). Results: The dose is verified by performing TLD and film dosimetry on the entrance and exit sides, as well as placing dosimeters inside the subjects. Both absolute doses and planar dose distributions have been determined providing an extensive set of data representing the dose within the subjects. Dose to critical organs was reduced by a factor of two in TMI cases. As a Result metabolic and cellular activities were reduced in TMI mice at the GI and brain compared to TBI mice. Bone marrow proliferation remains the same as bone marrow dose is unchanged. Conclusion: Properly characterized x‐ray beam, accurate dosimetry, and detailed molecular and cellular studies are of importance in radiobiology investigations in support of TMI model which may lead to new therapies for humans. Reduction in side effects such as GI toxicity from radiation is promising for transplantation. This project is supported by NIH.

Original languageEnglish (US)
Number of pages1
JournalMedical Physics
Volume40
Issue number6
DOIs
StatePublished - Jun 2013

Fingerprint

Benchmarking
Bone Marrow
Radiation
Brain
Film Dosimetry
X-Rays
Radiobiology
Lung
Molecular Imaging
Bromodeoxyuridine
Thymidine
Gastrointestinal Tract
Leukemia
Transplantation
Biomarkers
Transplants
Kidney
Liver

Cite this

WE‐E‐108‐08 : Dosimetric and Biological Benchmarking of a Murine Total Marrow Irradiation Platform. / Azimi, R.; Alaei, P.; Takahashi, Y.; Spezi, E.; Yagi, M.; Arentsen, L.; Sharkey, L.; Seelig, D.; Schappa, J.; Hui, S.

In: Medical Physics, Vol. 40, No. 6, 06.2013.

Research output: Contribution to journalArticle

@article{8eb347758b59488fb711c2cb03406551,
title = "WE‐E‐108‐08: Dosimetric and Biological Benchmarking of a Murine Total Marrow Irradiation Platform",
abstract = "Purpose: Increased radiation dose for recently developed clinical total marrow irradiation (TMI) facilitates bone marrow transplants for high risk leukemia patients but its mechanism and role is completely unknown. To initiate this high impact, clinically relevant, investigation, a murine TMI‐like system has been developed and benchmarked. Detailed dosimetric characterization of the irradiator, toxicity to critical organs, and molecular imaging biomarkers were evaluated. Methods: An orthovoltage x‐ray unit was commissioned and calibrated following TG‐61 protocol. A special irradiation jig utilizing compensators has been developed to reduce the dose to eyes, brain, lungs, heart, and gastrointestinal tract. Validation of the dosimetry has been performed using TLDs, Gafchromic film, ionization chamber, and Monte Carlo calculations. Mice were irradiated for TBI and TMI. Live and longitudinal pre and post radiation (day 2) FDG microPET/CT imaging was performed. Certain organs such as lungs, liver, kidney, gut and brain were harvested post radiation for the purpose of cellular and histological studies using thymidine analog 5‐bromo‐2‐deoxyuridine (BrdU). Results: The dose is verified by performing TLD and film dosimetry on the entrance and exit sides, as well as placing dosimeters inside the subjects. Both absolute doses and planar dose distributions have been determined providing an extensive set of data representing the dose within the subjects. Dose to critical organs was reduced by a factor of two in TMI cases. As a Result metabolic and cellular activities were reduced in TMI mice at the GI and brain compared to TBI mice. Bone marrow proliferation remains the same as bone marrow dose is unchanged. Conclusion: Properly characterized x‐ray beam, accurate dosimetry, and detailed molecular and cellular studies are of importance in radiobiology investigations in support of TMI model which may lead to new therapies for humans. Reduction in side effects such as GI toxicity from radiation is promising for transplantation. This project is supported by NIH.",
author = "R. Azimi and P. Alaei and Y. Takahashi and E. Spezi and M. Yagi and L. Arentsen and L. Sharkey and D. Seelig and J. Schappa and S. Hui",
year = "2013",
month = "6",
doi = "10.1118/1.4815586",
language = "English (US)",
volume = "40",
journal = "Medical Physics",
issn = "0094-2405",
publisher = "AAPM - American Association of Physicists in Medicine",
number = "6",

}

TY - JOUR

T1 - WE‐E‐108‐08

T2 - Dosimetric and Biological Benchmarking of a Murine Total Marrow Irradiation Platform

AU - Azimi, R.

AU - Alaei, P.

AU - Takahashi, Y.

AU - Spezi, E.

AU - Yagi, M.

AU - Arentsen, L.

AU - Sharkey, L.

AU - Seelig, D.

AU - Schappa, J.

AU - Hui, S.

PY - 2013/6

Y1 - 2013/6

N2 - Purpose: Increased radiation dose for recently developed clinical total marrow irradiation (TMI) facilitates bone marrow transplants for high risk leukemia patients but its mechanism and role is completely unknown. To initiate this high impact, clinically relevant, investigation, a murine TMI‐like system has been developed and benchmarked. Detailed dosimetric characterization of the irradiator, toxicity to critical organs, and molecular imaging biomarkers were evaluated. Methods: An orthovoltage x‐ray unit was commissioned and calibrated following TG‐61 protocol. A special irradiation jig utilizing compensators has been developed to reduce the dose to eyes, brain, lungs, heart, and gastrointestinal tract. Validation of the dosimetry has been performed using TLDs, Gafchromic film, ionization chamber, and Monte Carlo calculations. Mice were irradiated for TBI and TMI. Live and longitudinal pre and post radiation (day 2) FDG microPET/CT imaging was performed. Certain organs such as lungs, liver, kidney, gut and brain were harvested post radiation for the purpose of cellular and histological studies using thymidine analog 5‐bromo‐2‐deoxyuridine (BrdU). Results: The dose is verified by performing TLD and film dosimetry on the entrance and exit sides, as well as placing dosimeters inside the subjects. Both absolute doses and planar dose distributions have been determined providing an extensive set of data representing the dose within the subjects. Dose to critical organs was reduced by a factor of two in TMI cases. As a Result metabolic and cellular activities were reduced in TMI mice at the GI and brain compared to TBI mice. Bone marrow proliferation remains the same as bone marrow dose is unchanged. Conclusion: Properly characterized x‐ray beam, accurate dosimetry, and detailed molecular and cellular studies are of importance in radiobiology investigations in support of TMI model which may lead to new therapies for humans. Reduction in side effects such as GI toxicity from radiation is promising for transplantation. This project is supported by NIH.

AB - Purpose: Increased radiation dose for recently developed clinical total marrow irradiation (TMI) facilitates bone marrow transplants for high risk leukemia patients but its mechanism and role is completely unknown. To initiate this high impact, clinically relevant, investigation, a murine TMI‐like system has been developed and benchmarked. Detailed dosimetric characterization of the irradiator, toxicity to critical organs, and molecular imaging biomarkers were evaluated. Methods: An orthovoltage x‐ray unit was commissioned and calibrated following TG‐61 protocol. A special irradiation jig utilizing compensators has been developed to reduce the dose to eyes, brain, lungs, heart, and gastrointestinal tract. Validation of the dosimetry has been performed using TLDs, Gafchromic film, ionization chamber, and Monte Carlo calculations. Mice were irradiated for TBI and TMI. Live and longitudinal pre and post radiation (day 2) FDG microPET/CT imaging was performed. Certain organs such as lungs, liver, kidney, gut and brain were harvested post radiation for the purpose of cellular and histological studies using thymidine analog 5‐bromo‐2‐deoxyuridine (BrdU). Results: The dose is verified by performing TLD and film dosimetry on the entrance and exit sides, as well as placing dosimeters inside the subjects. Both absolute doses and planar dose distributions have been determined providing an extensive set of data representing the dose within the subjects. Dose to critical organs was reduced by a factor of two in TMI cases. As a Result metabolic and cellular activities were reduced in TMI mice at the GI and brain compared to TBI mice. Bone marrow proliferation remains the same as bone marrow dose is unchanged. Conclusion: Properly characterized x‐ray beam, accurate dosimetry, and detailed molecular and cellular studies are of importance in radiobiology investigations in support of TMI model which may lead to new therapies for humans. Reduction in side effects such as GI toxicity from radiation is promising for transplantation. This project is supported by NIH.

UR - http://www.scopus.com/inward/record.url?scp=85024804252&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85024804252&partnerID=8YFLogxK

U2 - 10.1118/1.4815586

DO - 10.1118/1.4815586

M3 - Article

AN - SCOPUS:85024804252

VL - 40

JO - Medical Physics

JF - Medical Physics

SN - 0094-2405

IS - 6

ER -