MnTnBuOE-2-PyP treatment protects from radioactive iodine (I-131) treatment-related side effects in thyroid cancer

Radiat Environ Biophys. 2020 Mar;59(1):99-109. doi: 10.1007/s00411-019-00820-2. Epub 2019 Nov 14.

Abstract

Treatment of differentiated thyroid cancer often involves administration of radioactive iodine (I-131) for remnant ablation or adjuvant therapy. However, there is morbidity associated with I-131 therapy, which can result in both acute and chronic complications. Currently, there are no approved radioprotectors that can be used in conjunction with I-131 to reduce complications in thyroid cancer therapy. It is well known that the damaging effects of ionizing radiation are mediated, in part, by the formation of reactive oxygen species (ROS). A potent scavenger of ROS, Mn(III)meso-tetrakis(N-n-butoxyethylpyridinium-2-yl)porphyrin (MnTnBuOE-2-PyP), has radioprotective and anti-tumor effects in various cancer models including head and neck, prostate, and brain tumors exposed to external beam radiation therapy. Female C57BL/6 mice were administered I-131 orally at doses of 0.0085-0.01 mCi/g (3.145 × 105 to 3.7 × 105 Bq) of body weight with or without MnTnBuOE-2-PyP. We measured acute external inflammation, blood cell counts, and collected thyroid tissue and salivary glands for histological examination. We found oral administration of I-131 caused an acute decrease in platelets and white blood cells, caused facial swelling, and loss of thyroid and salivary tissues. However, when MnTnBuOE-2-PyP was given during and after I-131 administration, blood cell counts remained in the normal range, less facial inflammation was observed, and the salivary glands were protected from radiation-induced killing. These data indicate that MnTnBuOE-2-PyP may be a potent radioprotector of salivary glands in thyroid cancer patients receiving I-131 therapy.

Keywords: MnTnBuOE-2-PyP; Radioactive iodine; Radioprotector; Thyroid cancer.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Female
  • Humans
  • Iodine Radioisotopes / adverse effects*
  • Metalloporphyrins / pharmacology
  • Metalloporphyrins / therapeutic use*
  • Mice, Inbred C57BL
  • Radiation-Protective Agents / pharmacology
  • Radiation-Protective Agents / therapeutic use*
  • Radiopharmaceuticals / adverse effects*
  • Salivary Glands / drug effects
  • Salivary Glands / pathology
  • Salivary Glands / radiation effects
  • Thyroid Gland / drug effects
  • Thyroid Gland / pathology
  • Thyroid Gland / radiation effects
  • Thyroid Neoplasms / pathology
  • Thyroid Neoplasms / radiotherapy*

Substances

  • Iodine Radioisotopes
  • Iodine-131
  • Metalloporphyrins
  • Mn(III) meso-tetrakis(N-n-butoxyethylpyridinium-2-yl)porphyrin
  • Radiation-Protective Agents
  • Radiopharmaceuticals