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


METHODS
Twenty-seven women were scanned with (99m)TcO(4)(-) or (123)I(-) to assess NIS activity in their metastases. An (131)I 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 I(-) uptakes were decreased to </=2.8% 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 (131)I 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 (131)I 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 (131)I-radioablation of BCM possible with negligible thyroid uptake and radiation damage.
Wapnir
Irene L
IL
Department of Surgery, Stanford University School of Medicine, Stanford, California, USA. wapnir@stanford.edu
Goris
Michael
M
Yudd
Anthony
A
Dohan
Orsolya
O
Adelman
Donna
D
Nowels
Kent
K
Carrasco
Nancy
N
D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007454:Iodides / Q000493:pharmacokinetics*; D009362:Neoplasm Metastasis; D009369:Neoplasms; D011874:Radiometry; D011877:Radionuclide Imaging; D027981:Symporters / Q000378:metabolism / Q000502:physiology*; D013961:Thyroid Gland / Q000473:pathology / Q000528:radiation effects; D013964:Thyroid Neoplasms / Q000378:metabolism; D013997:Time Factors; D014284:Triiodothyronine / Q000378:metabolism; D000099209:Sodium-Iodide Symporters
D007454:Iodides; D027981:Symporters; D014284:Triiodothyronine; D000099209:Sodium-Iodide Symporters