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Published on: March 13, 2018
Relationship between apoptosis imaging and radioiodine therapy in tumor cells with different sodium iodide symporter
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.
Insights
Radioiodine therapy efficacy varies. Apoptosis imaging, not just iodine uptake, better predicts therapeutic outcomes for sodium iodide symporter-expressing cancers.
Area of Science:
- Oncology
- Nuclear Medicine
- Molecular Imaging
Background:
- Radioiodine (¹³¹I) therapy efficacy in cancer treatment shows significant variability.
- Sodium iodide symporter (NIS) expression levels do not reliably predict therapeutic response.
- Novel strategies are needed to accurately predict ¹³¹I therapy effectiveness.
Purpose of the Study:
- To investigate the correlation between iodine (I) uptake, apoptosis imaging, and therapeutic efficacy of radioiodine therapy.
- To compare the predictive value of iodine uptake imaging versus apoptosis imaging for treatment outcomes.
Main Methods:
- Established two HT29 cell lines with varying sodium iodide symporter (NIS) expression (CMV-NIS and TERT-NIS).
- Quantified iodine uptake using I-uptake assays and gamma camera imaging.
- Assessed apoptosis using confocal microscopy and a fluorescence imaging system with ApoFlamma (ApoPep-1).
- Determined therapeutic efficacy by measuring tumor size reduction in xenograft models.
Main Results:
- CMV-NIS cells exhibited higher iodine uptake and ApoFlamma signals compared to TERT-NIS cells.
- In vivo, CMV-NIS xenografts showed elevated technetium and ApoFlamma signals.
- Tumor reduction correlated more strongly with apoptosis imaging signals than with iodine uptake imaging.
- Higher NIS expression was associated with increased apoptosis, iodine uptake, and significant tumor reduction.
Conclusions:
- Apoptosis imaging, using agents like ApoFlamma, provides a more accurate prediction of radioiodine therapy efficacy than standard iodine uptake imaging.
- Targeting and imaging apoptosis may offer a superior strategy for predicting and monitoring therapeutic response in NIS-expressing cancers.
