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

Abstract

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.