Bioluminescent Monitoring of NIS-Mediated 131 I Ablative Effects in MCF-7 Xenografts

Optical imaging has made it possible to monitor response to anticancer therapies in tumor xenografts. The concept of treating breast cancers with 131I is predicated on the expression of the Na+/I− symporter (NIS) in many tumors and uptake of I in some. The pattern of 131I 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 131I 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 131I-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 131I-treated tumors increased after Day 22, corresponding to tumor regrowth. By Day 35, treated tumors were smaller and accumulated 33% less 99mTcO4 than untreated tumors. NIS immunoreactivity was present in <50% of 131I-treated cells compared to 85–90% of controls. In summary, a pattern of tumor regression occurring over the first three weeks after 131I administration was observed in NIS-expressing breast cancer xenografts