Treatment with rhenium-188-perrhenate and iodine-131 of NIS-expressing mammary cancer in a mouse model remarkably inhibited tumor growth

Ekaterina Dadachova, Andrew Nguyen, Elaine Y. Lin, Leo Gnatovskiy, Ping Lu, Jeffrey W. Pollard

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Introduction: Novel therapeutic modalities are needed for breast cancer patients in whom standard treatments are not effective. Mammary gland sodium/iodide symporter has been identified as a molecular target in breast cancers in humans and in some transgenic mouse models. We report the results of a therapy study with 131I- and 188ReO 4- of breast cancer in polyoma middle T oncoprotein (PyMT) transgenic mice endogenously expressing the Na+/I- symporter (NIS). Methods: PyMT mice (12-13 weeks old) with one palpable tumor of 0.5-0.8 cm in diameter were used. For the therapy studies, PyMT mice were (1) treated with two intraperitoneal injections of 1.5 mCi of 188ReO 4- 1 week apart, (2) pretreated for 1 week with 5 μg of triiodothyronine (T3) followed by two intraperitoneal injections of 1.5 mCi of 131I- 1 week apart or (3) left untreated. The tumor and normal organ uptakes were assessed by scintigraphic imaging. The thyroid function of treated and control animals was evaluated at the completion of the study by measuring the T3/thyroxine (T4) ratio in their blood. Results: There was significant uptake of 131I- and 188ReO 4- in the primary palpable tumors as well as in nonpalpable tumors, stomachs and thyroids. The tumor uptake after the second injection was 10 times lower in comparison with the first injection. Tumor growth was significantly inhibited in both the 131I- and 188ReO4- groups in comparison with the control group, and tumors in the 188ReO4- group increased in size significantly less than in the 131I- group. The T3/T4 ratios were calculated to be 27 and 25 for the control group and the 188ReO4- group, respectively; for 131I-, both the T3 and T4 levels were below detection limit, demonstrating much less effect on the thyroids of treatment with 188ReO4- than with 131I-. Conclusions: These results prove that NIS expression in breast tumors in animal models allows specific, efficient and safe treatment with a variety of radionuclides transported by NIS.

Original languageEnglish (US)
Pages (from-to)695-700
Number of pages6
JournalNuclear Medicine and Biology
Volume32
Issue number7
DOIs
StatePublished - Oct 2005

Fingerprint

Rhenium
Symporters
Iodine
Breast Neoplasms
Growth
Oncogene Proteins
Neoplasms
Thyroid Gland
Intraperitoneal Injections
Transgenic Mice
Therapeutics
Control Groups
Injections
Triiodothyronine
Human Mammary Glands
perrhenate
Thyroxine
Radioisotopes
Limit of Detection
Stomach

Keywords

  • Breast cancer
  • Iodine-131
  • NIS
  • PyMT mouse model
  • Rhenium-188
  • Therapy

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging

Cite this

Treatment with rhenium-188-perrhenate and iodine-131 of NIS-expressing mammary cancer in a mouse model remarkably inhibited tumor growth. / Dadachova, Ekaterina; Nguyen, Andrew; Lin, Elaine Y.; Gnatovskiy, Leo; Lu, Ping; Pollard, Jeffrey W.

In: Nuclear Medicine and Biology, Vol. 32, No. 7, 10.2005, p. 695-700.

Research output: Contribution to journalArticle

Dadachova, Ekaterina ; Nguyen, Andrew ; Lin, Elaine Y. ; Gnatovskiy, Leo ; Lu, Ping ; Pollard, Jeffrey W. / Treatment with rhenium-188-perrhenate and iodine-131 of NIS-expressing mammary cancer in a mouse model remarkably inhibited tumor growth. In: Nuclear Medicine and Biology. 2005 ; Vol. 32, No. 7. pp. 695-700.
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AU - Gnatovskiy, Leo

AU - Lu, Ping

AU - Pollard, Jeffrey W.

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N2 - Introduction: Novel therapeutic modalities are needed for breast cancer patients in whom standard treatments are not effective. Mammary gland sodium/iodide symporter has been identified as a molecular target in breast cancers in humans and in some transgenic mouse models. We report the results of a therapy study with 131I- and 188ReO 4- of breast cancer in polyoma middle T oncoprotein (PyMT) transgenic mice endogenously expressing the Na+/I- symporter (NIS). Methods: PyMT mice (12-13 weeks old) with one palpable tumor of 0.5-0.8 cm in diameter were used. For the therapy studies, PyMT mice were (1) treated with two intraperitoneal injections of 1.5 mCi of 188ReO 4- 1 week apart, (2) pretreated for 1 week with 5 μg of triiodothyronine (T3) followed by two intraperitoneal injections of 1.5 mCi of 131I- 1 week apart or (3) left untreated. The tumor and normal organ uptakes were assessed by scintigraphic imaging. The thyroid function of treated and control animals was evaluated at the completion of the study by measuring the T3/thyroxine (T4) ratio in their blood. Results: There was significant uptake of 131I- and 188ReO 4- in the primary palpable tumors as well as in nonpalpable tumors, stomachs and thyroids. The tumor uptake after the second injection was 10 times lower in comparison with the first injection. Tumor growth was significantly inhibited in both the 131I- and 188ReO4- groups in comparison with the control group, and tumors in the 188ReO4- group increased in size significantly less than in the 131I- group. The T3/T4 ratios were calculated to be 27 and 25 for the control group and the 188ReO4- group, respectively; for 131I-, both the T3 and T4 levels were below detection limit, demonstrating much less effect on the thyroids of treatment with 188ReO4- than with 131I-. Conclusions: These results prove that NIS expression in breast tumors in animal models allows specific, efficient and safe treatment with a variety of radionuclides transported by NIS.

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