The Na+/I- symporter mediates iodide uptake in breast cancer metastases and can be selectively down-regulated in the thyroid

Purpose: The Na+/I- symporter (NIS) is a key plasma membrane protein that mediates active iodide (I-) transport in the thyroid, lactating breast, and other tissues. Functional NIS expression in thyroid cancer accounts for the longstanding success of radioactive iodide (I-131) ablation of metastases after thyroidectomy. Breast cancer is the only other cancer demonstrating endogenous functional NIS expression. Until now, NIS activity in breast cancer metastases (BCM) was unproven. Experimental Design: Twenty-seven women were scanned with (TcO4-)-Tc-99m or I-123(-) to assess NIS activity in their metastases. An I-131 dosimetry study was offered to patients with I--accumulating tumors. Selective down-regulation of thyroid NIS was tested in 13 patients with T-3 and in one case with T-3 + methimazole (MMI; blocks I- organification). NIS expression was evaluated in index and/or metastatic tumor samples by immunohistochemistry. Results: I- uptake was noted in 25% of NIS-expressing tumors (two of eight). The remaining cases did not show NIS expression or activity. Thyroid F uptakes were decreased to less than or equal to2.8% at 24 h in T-3-treated patients and 1/100 normal with T-3/MMI. Uptake (2.9%) was calculated in a peribronchial metastasis on I-131 dosimetry scans at 4 h with disappearance of the signal by 24 h. We estimated a therapeutic dose of 3000 cGy could be achieved in this metastasis with 100 mCi of I-131 if the tumor exhibited the same dynamics as the T-3/MMI-suppressed thyroid. Conclusions: This is the first article of in vivo, scintigraphically detected, NIS-mediated I- accumulation in human BCM. T-3/MMI down-regulation of thyroid NIS makes I-131-radioahlation of BCM possible with negligible thyroid uptake and radiation damage.