Evaluation of hyperpolarized [1-¹³C]-pyruvate by magnetic resonance to detect ionizing radiation effects in real time.
Ionizing radiation (IR) cytotoxicity is primarily mediated through reactive oxygen species (ROS). Since tumor cells neutralize ROS by utilizing reducing equivalents, we hypothesized that measurements of reducing potential using real-time hyperpolarized (HP) magnetic resonance spectroscopy (MRS) and spectroscopic imaging (MRSI) can serve as a surrogate marker of IR induced ROS. This hypothesis was tested in a pre-clinical model of anaplastic thyroid carcinoma (ATC), an aggressive head and neck malignancy. Human ATC cell lines were utilized to test IR effects on ROS and reducing potential in vitro and [1-¹³C] pyruvate HP-MRS/MRSI imaging of ATC orthotopic xenografts was used to study in vivo effects of IR. IR increased ATC intra-cellular ROS levels resulting in a corresponding decrease in reducing equivalent levels. Exogenous manipulation of cellular ROS and reducing equivalent levels altered ATC radiosensitivity in a predictable manner. Irradiation of ATC xenografts resulted in an acute drop in reducing potential measured using HP-MRS, reflecting the shunting of reducing equivalents towards ROS neutralization. Residual tumor tissue post irradiation demonstrated heterogeneous viability. We have adapted HP-MRS/MRSI to non-invasively measure IR mediated changes in tumor reducing potential in real time. Continued development of this technology could facilitate the development of an adaptive clinical algorithm based on real-time adjustments in IR dose and dose mapping.
Bobby R. Alford Department of Otolaryngology, Head and Neck Surgery, Baylor College of Medicine, Houston, Texas, United States of America ; Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.
Vlad C
VC
Sandulache
Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.
Yunyun
Y
Chen
Department of Imaging Physics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.
Jaehyuk
J
Lee
Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Ashley
A
Rubinstein
Department of Imaging Physics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.
Marc S
MS
Ramirez
Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.
Heath D
HD
Skinner
Department of Imaging Physics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.
Christopher M
CM
Walker
Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
Michelle D
MD
Williams
Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Ramesh
R
Tailor
Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Laurence E
LE
Court
Department of Imaging Physics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.
James A
JA
Bankson
Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America ; Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States of America.
Stephen Y
SY
Lai
D000818:Animals; D002247:Carbon Isotopes / Q000737:chemistry*; D045744:Cell Line, Tumor; D004307:Dose-Response Relationship, Radiation; D005434:Flow Cytometry; D005452:Fluoresceins; D064593:Heterografts / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008819:Mice, Nude; D010084:Oxidation-Reduction / Q000528:radiation effects; D019289:Pyruvic Acid / Q000737:chemistry*; D011839:Radiation, Ionizing; D017382:Reactive Oxygen Species / Q000378:metabolism*; D065646:Thyroid Carcinoma, Anaplastic; D013964:Thyroid Neoplasms / Q000532:radiotherapy*
C110400:2',7'-dichlorodihydrofluorescein diacetate; D002247:Carbon Isotopes; D005452:Fluoresceins; D017382:Reactive Oxygen Species; D019289:Pyruvic Acid