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Iodine and the Body

 

Iodine and the Breast  

Wapnir

 

Bioluminescent monitoring of NIS-mediated (131)I ablative effects in MCF-7 xenografts.

Ghosh M, Gambhir SS, De A, Nowels K, Goris M, Wapnir I.

Mol Imaging. 2006 Apr-Jun;5(2):76-84.

[abstract only]

 

"Optical imaging has made it possible to monitor response to anticancer therapies in tumor xenografts. The concept of treating breast cancers with (131)I is predicated on the expression of the Na(+)/I- symporter (NIS) in many tumors and uptake of I- in some. The pattern of (131)I radioablative effects were investigated in an MCF-7 xenograft model dually transfected with firefly luciferase and NIS genes. On Day 16 after tumor cell implantation, 3 mCi of (131)I was injected. Bioluminescent imaging using d-luciferin and a cooled charge-coupled device camera was carried out on Days 1, 2, 3, 7, 10, 16, 22, 29, and 35. Tumor bioluminescence decreased in (131)I-treated tumors after Day 3 and reached a nadir on Day 22. Conversely, bioluminescence steadily increased in controls and was 3.85-fold higher than in treated tumors on Day 22. Bioluminescence in (131)I-treated tumors increased after Day 22, corresponding to tumor regrowth. By Day 35, treated tumors were smaller and accumulated 33% less (99m)TcO(4)(-) than untreated tumors. NIS immunoreactivity was present in <50% of (131)I-treated cells compared to 85-90% of controls. In summary, a pattern of tumor regression occurring over the first three weeks after (131)I administration was observed in NIS-expressing breast cancer xenografts."

 

 

Immunohistochemical profile of the sodium/iodide symporter in thyroid, breast, and other carcinomas using high density tissue microarrays and conventional sections.

Wapnir IL, van de Rijn M, Nowels K, Amenta PS, Walton K, Montgomery K, Greco RS, Dohan O, Carrasco N.

J Clin Endocrinol Metab. 2003 Apr;88(4):1880-8.

 

"Extrathyroidal cancers could potentially be targeted with (131)I, if the Na(+)/I(-) symporter (NIS) were functional. Using immunohistochemical methods we probed 1278 human samples with anti-NIS antibody, including 253 thyroid and 169 breast conventional whole tissue sections (CWTS). Four high density tissue microarrays containing a wide variety of breast lesions, normal tissues, and carcinoma cores were tested. The results of the normal microarray were corroborated in 50 CWTS. Nineteen of 34 normal tissues, including bladder, colon, endometrium, kidney, prostate, and pancreas, expressed NIS. Nineteen of 25 carcinomas demonstrated NIS immunopositivity; 55.7% of 479 carcinoma microarray cores expressed NIS, including prostate (74%), ovary (73%), lung (65%), colon (62.6%), and endometrium (56%). NIS protein was present in 75% benign thyroid lesions, 73% thyroid cancers, 30% normal-appearing, peritumoral breasts, 88% ductal carcinomas in situ, and 76% invasive breast carcinoma CWTS. Comparatively, breast microarray cores had lower immunoreactivity. Plasma membrane immunopositivity was confirmed in thyrocytes, salivary ductal, gastric mucosa, and lactating mammary cells. In other tissues, immunoreactivity was predominantly intracellular, particularly in malignant lesions. Thus, NIS is present in many normal epithelial tissues and is predominantly expressed intracellularly in many carcinomas. Elucidating the regulatory mechanisms that render NIS functional in extrathyroidal carcinomas may make (131)I therapy feasible."

 

 

Selective Targeting of Breast Cancer with Radioiodide

Wapnir I

Research Award -- 2001-2004.  $315,200

 

"Final Report (2004) Background: Initial studies pioneered by our group identified an iodide-carrier protein, called NIS (sodium/iodide symporter), in milk-producing breast cells and in approximately 70% of human breast cancers. Iodide transport has been primarily linked to the thyroid gland where it is integrated into the production of thyroid hormones. Radioiodides can be used to visualize iodide-transporting tissues or to destroy them with a radioactive form of iodide (131I). Discovering the presence of the same protein in breast tissues generated great enthusiasm, because of the possibility of translating the success of 131I therapy in thyroid cancer to breast cancer. The likelihood that NIS could be used to selectively target and destroy breast cancer cells without targeting the thyroid was enhanced by our observations that lactation-associated hormones (estrogen, prolactin and oxytocin) governed NIS production and activity in the non-pregnant breast cell. In contrast, thyroid NIS is regulated by thyroid stimulating hormone and iodide accumulation can be blocked with thyroid hormones."
 

"Future direction and impact: These experiments allowed us to establish an experimental platform (animal model) prior to more clinically-directed studies. We gained important insights into understanding what factors are likely to influence NIS production and activity in breast cancer. Our results are “proof of principle” that the iodide-carrier NIS protein can be exploited for the selective targeting and destruction of breast cancers. In summary, we believe that it will be possible to harness the iodide-concentrating capacity of NIS positive breast cancers for an innovative therapeutic approach. Furthermore, it may also be possible to either modulate or activate this mechanism in breast cancer cells that lack NIS. Because of prior clinical work in treating thyroid cancers, radioactive iodide could be, (i) less toxic, (ii) individually tailored, and (iii) easy to administer to breast cancer patients. It could provide many women with an alternative strategy to combat this deadly disease."

 

 

More articles by Wapnir and Carrasco

 
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