Abstract
The therapeutic efficacy of radioiodine (¹³¹I) therapy has been reported to be variable among cancer patients and even between metastatic regions in the same patients. Because the expression level of sodium iodide symporter (NIS) cannot reflect the efficacy of therapy, other strategies are required to predict the precise therapeutic effect of ¹³¹I therapy. In this research, we investigated the correlation between iodine (I) uptake, apoptosis imaging, and therapeutic efficacy. Two HT29 cell lines, cytomegalovirus (CMV)-NIS (or NIS+++) and TERT-NIS (or NIS+), were established by retroviral transfection. I uptake was estimated by I-uptake assay and gamma camera imaging. Apoptosis was evaluated by confocal microscopy and a Maestro fluorescence imaging system (CRi Inc., Woburn, MA) using ApoFlamma (BioACTs, Seoul, Korea), a fluorescent dye-conjugated apoptosis-targeting peptide 1 (ApoPep-1). Therapeutic efficacy was determined by tumor size. The CMV-NIS showed higher I uptake and ApoFlamma signals than TERT-NIS. In xenograft models, CMV-NIS also showed high 99m technetium signals and ApoFlamma signals. Tumor reduction had a stronger correlation with apoptosis imaging signals than with gamma camera imaging signals, which reflect I uptake. Higher NIS-expressing tumors showed increased apoptosis and I uptake, resulting in a significant tumor reduction. Moreover, tumor reduction showed a strong correlation with ApoFlamma imaging compared to I-uptake imaging.
Highlights
R ADIOIODINE (131I) has been effectively used in patients with differentiated thyroid carcinomas for more than 70 years.[1]
131I-treated cells in CMV-NIS cells (Figure 2B) had more intense ApoFlamma fluorescent signals compared to untreated cells. These results indicate that apoptosis occurred more vigorously in tumor cells with high levels of NIS expression (CMV-NIS) compared to those with low levels of NIS expression (TERT-NIS)
55% of ApoFlamma-positive cells were observed in cells with CMV-NIS after 24 hours of 131I treatment, whereas only 1% of ApoFlamma-positive cells were observed in cells with TERT-NIS
Summary
R ADIOIODINE (131I) has been effectively used in patients with differentiated thyroid carcinomas for more than 70 years.[1]. The relationship between cellular NIS expression and the therapeutic effect of 131I has been studied to improve the efficacy of 131I therapy.[2,3]. But 8% of the tumors showed aggressive characteristics.[5] NIS expression seems to provide important information on the therapeutic effect of 131I. As apoptosis is an essential process in cancer therapy,[9] apoptosis imaging provides important prognostic information.[10] annexin V has been widely used for apoptosis imaging in clinical circumstances, annexin V, which targets phosphatidylserine in the inner leaflet of cell membrane, has many disadvantages in terms of a lack of specificity for apoptotic cells to nonapoptotic cells, slow removal from the body, and a low signal to background ratio for in vivo practice.[11,12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
