NIS and epithelial-mesenchymal transition marker expression of circulating tumor cells for predicting and monitoring the radioactive iodine-131 therapy effect in differentiated thyroid cancers.

Current methods, such as serum thyroglobulin measurement and medical imaging, have limitations in the routine monitoring of the disease status and treatment response of patients with differentiated thyroid cancers (DTCs), and additional methods remain to be explored. The aim of this study was to investigate the clinical value of the sodium/iodide symporter (NIS) expression and epithelial-mesenchymal transition (EMT) phenotypes of circulating tumor cells (CTCs) in monitoring the disease status and treatment response of DTC. Blood samples were obtained from DTC patients before (1 to 3 months after total thyroidectomy) and 4 to 6 months after radioactive iodine-131 (RAI) therapy for the CTC assessments. The number, NIS expression, and EMT phenotypes of CTCs were enumerated and characterized with CanPatrol™ CTC enrichment and mRNA in situ hybridization. Postoperative NIS high expression was independently correlated with a better response to first RAI therapy and good treatment efficacy. Postoperative NIS-/epithelial-/mesenchymal+ CTCs presence was independently correlated with a worse response to first RAI therapy. The numbers of total NIS+ CTCs and NIS+/epithelial+/mesenchymal+ CTCs after first RAI therapy were negatively correlated with a better response to RAI therapy only in univariate analyses. Univariate and multivariate analyses showed that a decreased or unchanged number of total NIS+ CTCs after RAI therapy may denote good efficacy and effective RAI therapy. These preliminary data suggest that assessment of the NIS expression and EMT phenotypes of CTCs may serve as potential adjuncts for predicting and monitoring the curative effect of RAI therapy in DTC patients and avoid ineffective treatment. Further validation is warranted.

Imaging targeted at tumor with (188)Re-labeled VEGF(189) exon 6-encoded peptide and effects of the transfecting truncated KDR gene in tumor-bearing nude mice.

INTRODUCTION: Planar imaging of (188)Re-labeled vascular endothelial growth factor (VEGF)(189) exon 6-encoded peptide (QKRKRKKSRYKS) with single photon emission computed tomography (SPECT) in tumor-bearing nude mice and effects of the transfecting truncated KDR gene on its imaging were investigated, so as to provide a basis for further applying the peptide to tumor-targeted radionuclide treatment. METHODS: QKRKRKKSRYKS, coupling with mercaptoacetyltriglycine (MAG(3)) chelator was labeled with (188)Re; then in vivo distribution, planar imaging with SPECT and blocking experiment in tumor-bearing nude mice were analyzed. Recombinant adenovirus vectors carrying the truncated KDR gene were constructed to transfect tumor tissues to evaluate the effects of truncated KDR on the in vivo distribution and tumor planar imaging of (188)Re-MAG(3)-QKRKRKKSRYKS in tumor-bearing nude mice. RESULTS: The labeled peptide exhibited a sound receptor binding activity. Planar imaging with SPECT demonstrated significant radioactivity accumulation in tumor 1 h after injection of the labeled peptide and disappearance of radioactivity 3 h later. Significant radioactivity accumulation was also observed in the liver, intestines and kidneys but was not obvious in other tissues. An hour after injection of the labeled peptide, the percentage of the injected radioactive dose per gram (%ID/g) of tumor and tumor/contralateral muscle tissues ratio were 1.98+/-0.38 and 2.53+/-0.33, respectively, and increased to 3.08+/-0.84 and 3.61+/-0.59 in the group transfected with the truncated KDR gene, respectively, and radioactivity accumulation in tumor with planar imaging also increased significantly in the transfection group. CONCLUSION: (188)Re-MAG(3)-QKRKRKKSRYKS can accumulate in tumor tissues, which could be increased by the transfection of truncated KDR gene. This study provides a basis for further applying the peptide to tumor targeted radionuclide imaging and treatment.