Differential radiation protection of salivary glands versus tumor by tempol with accompanying tissue assessment of tempol by magnetic resonance imaging

Ana P. Cotrim, Fuminori Hyodo, Ken Ichiro Matsumoto, Anastasia L. Sowers, John A. Cook, Bruce J. Baum, Murali C. Krishna, James B. Mitchell

研究成果: Contribution to journalArticle査読

88 被引用数 (Scopus)

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Purpose: The nitroxide free radical, Tempol, was evaluated for potential differential radiation protection of salivary glands and tumor using fractionated radiation. Mechanistic information was explored by monitoring the presence and bioreduction of Tempol in both tissues noninvasively by magnetic resonance imaging (MRI). Experimental Design: Female C3H mice were immobilized using custom-made Lucite jigs for localized irradiation (five daily fractions) either to the oral cavity or tumor-bearing leg. Tempol (275 mg/kg)was administered (i.p.) 10 min before each radiation fraction. Salivary gland damage was assessed 8 weeks after radiation by measuring pilocarpine-mediated saliva output. Tumor growth was assessed by standard radiation regrowth methods. Dynamic T1-weighted magnetic resonance scans were acquired before and after Tempol injection using a 4.7T animal MRI instrument. Results: Tempol treatment was found to protect salivary glands significantly against radiation damage (∼60% improvement); whereas no tumor protection was observed. Intracellular reduction of Tempol to the nonradioprotective hydroxylamine as assessed by MRI was 2-fold faster in tumor compared with salivary glands or muscle. Conclusions: Tempol provided salivary gland radioprotection and did not protect tumor, consistent with the hypothesis that differential radioprotection by Tempol resides in faster reduction to the nonradioprotective hydroxylamine in tumor compared with normal tissues. The unique paramagnetic properties of Tempol afforded noninvasive MRI monitoring of dynamic changes of Tempol levels in tissue to support the finding. These data support further development and consideration of Tempol for human clinical trials as a selective protector against radiation-induced salivary gland damage.

本文言語英語
ページ(範囲)4928-4933
ページ数6
ジャーナルClinical Cancer Research
13
16
DOI
出版ステータス出版済み - 8 15 2007
外部発表はい

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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