Regression of experimental NIS-expressing breast cancer brain metastases in response to radioiodide/gemcitabine dual therapy

Renier, Corinne; Do, J.; Reyna-Neyra, Andrea; Foster, Deshka S.; De, Abhijit; Vogel, Hannes; Jeffrey, Stefanie S.; Tse, Victor; Carrasco, Nancy; Wapnir, Irene

doi:10.18632/oncotarget.10238

Cited by 8 publications

(5 citation statements)

References 47 publications

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“…Accordingly, NIS is a preferred tool in new targeted modalities, such as adenovirus and oncolytic virus therapy, stem cell therapy and regenerative medicine , Montiel-Equihua et al 2008, Baril et al 2010, Riesco-Eizaguirre et al 2011. RAI may also be successful for extrathyroidal endogenous NIS-overexpressing tumors such as in breast (Tazebay et al 2000, Renier et al 2016 and ovarian cancer (Riesco-Eizaguirre et al 2014) (Fig. 4).…”

Section: Nismentioning

confidence: 99%

Role of iodide metabolism in physiology and cancer

Vieja¹,

Santisteban²

2018

Endocrine-Related Cancer

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Iodide (I) metabolism is crucial for the synthesis of thyroid hormones (THs) in the thyroid and the subsequent action of these hormones in the organism. I is principally transported by the sodium iodide symporter (NIS) and by the anion exchanger PENDRIN, and recent studies have demonstrated the direct participation of new transporters including anoctamin 1 (ANO1), cystic fibrosis transmembrane conductance regulator (CFTR) and sodium multivitamin transporter (SMVT). Several of these transporters have been found expressed in various tissues, implicating them in I recycling. New research supports the exciting idea that I participates as a protective antioxidant and can be oxidized to hypoiodite, a potent oxidant involved in the host defense against microorganisms. This was possibly the original role of I in biological systems, before the appearance of TH in evolution. I per se participates in its own regulation, and new evidence indicates that it may be antineoplastic, anti-proliferative and cytotoxic in human cancer. Alterations in the expression of I transporters are associated with tumor development in a cancer-type-dependent manner and, accordingly, NIS, CFTR and ANO1 have been proposed as tumor markers. Radioactive iodide has been the mainstay adjuvant treatment for thyroid cancer for the last seven decades by virtue of its active transport by NIS. The rapid advancement of techniques that detect radioisotopes, in particular I, has made NIS a preferred target-specific theranostic agent.

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Section: Nismentioning

confidence: 99%

Role of iodide metabolism in physiology and cancer

Vieja¹,

Santisteban²

2018

Endocrine-Related Cancer

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“…Breast cancer cells express the NIS (30), which uses the transmembrane sodium ion concentration gradient as the primary driving force to transport iodine into cells (31)(32)(33). Therefore, this protein provides a new target for improving radioiodine treatment of breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Synthesis and application of 131I-fulvestrant as a targeted radiation drug for endocrine therapy in human breast cancer

et al. 2018

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The aim of this study was to label fulvestrant (an endocrine therapy drug for breast cancer) with radioiodine and to evaluate the effect of 131I-fulvestrant on inhibiting the growth of human breast cancer and its influence on major organs in nude mice. Fulvestrant was labeled with radioiodine using a modified chloramine T method, and its chemical properties were assessed using traditional methods. The binding affinity of 131I-fulvestrant was measured by radioligand binding assays, and its antiproliferative activity was determined by MTT assays. The ability of 131I-fulvestrant to kill MCF-7 and MDA-MB-231 cells was also detected by MTT assays. We established MCF-7 cell xenografts in nude mice and monitored tumor growth and critical organ function. When the labeling reactions were conducted for 5 min at room temperature at pH 7.5, the radiochemical yield of the 131I labeling to fulvestrant was 62.34±1.8%, the radiochemical purity was 98.6±3.4%, and the half maximal inhibitory concentration (IC50) at 48 h was 35 µCi. 131I-fulvestrant was stable, and its binding affinity to estrogen receptor-positive (ER+) MCF-7 cells was also retained. In addition, 131I-fulvestrant exhibited similar cytotoxicity in MCF-7 and MDA-MB-231 cells, although MCF-7 cells showed a slightly more pronounced response. 131I-fulvestrant continuously exerted a tumor suppressive effect on MCF-7 cells but not on MDA-MB-231 cells (P<0.05). Upon intravenous injection of 131I-fulvestrant into nude mice, the radioactivity distribution corresponded to ER expression patterns and was primarily confined to the tumor. 131I-fulvestrant exhibited a precise growth inhibition effect on MCF-7 breast cancer cells, and its effects on general conditions of nude mice and their major organs were manageable. Therefore, radioiodine labeling of fulvestrant was successful and could be used to develop novel drugs for breast cancer by superimposing the benefits of radiotherapy and endocrine therapy.

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“…Eine der ersten nicht thyreoidalen Tumorentitäten, in denen eine Expression des NIS gezeigt wurde (mRNA-Expression auf immunhistologischen Färbungen), war das Mammakarzinom [17,18]. Daher spekulierten einige Arbeitsgruppen, dass das metastasierte Mammakarzinom mit Radiojod behandelt werden könne.…”

Section: Radiojod Bei Mammakarzinomunclassified

124J/131J-Theranostik des Natrium-Jodid-Symporters beim Schilddrüsenkarzinom

et al. 2019

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ZusammenfassungEines der vielversprechendsten Konzepte in der Nuklearmedizin ist die Theranostik, die im Wesentlichen die Diagnostik und Therapie eines bestimmten Targets beinhaltet, insbesondere, wenn es darum geht, Krebstherapien zu optimieren und zu individualisieren. In der Nuklearmedizin werden Theranostika bereits seit über 60 Jahren in der klinischen Routine mit 131J/123J für diagnostische und therapeutische Zwecke bei Schilddrüsenerkrankungen eingesetzt. Dieser Artikel gibt einen kurzen Überblick über die Verwendung von 2 Radiojod-Isotopen (131J und 124J) für das Targeting des Natrium-Jodid-Symporters bei Schilddrüsenkarzinomen und nicht thyreoidalen Tumoren. Insbesondere wird die Rolle der 124J-basierten Dosimetrie diskutiert. Abschließend zeigen wir an einem Patientenbeispiel, wie die Expression des Natrium-Jodid-Symporters bei einem Patienten mit Radiojod-refraktärem fortgeschrittenem Schilddrüsenkarzinom durch Medikamente manipuliert werden kann.

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Regression of experimental NIS-expressing breast cancer brain metastases in response to radioiodide/gemcitabine dual therapy

Cited by 8 publications

References 47 publications

Role of iodide metabolism in physiology and cancer

Role of iodide metabolism in physiology and cancer

Synthesis and application of 131I-fulvestrant as a targeted radiation drug for endocrine therapy in human breast cancer

124J/131J-Theranostik des Natrium-Jodid-Symporters beim Schilddrüsenkarzinom

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