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A Novel Approach for Image-Guided

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Summary
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Mesenchymal stem cells (MSC) engineered to carry the sodium iodide symporter (NIS) gene effectively target pancreatic tumors. This NIS gene delivery via MSCs enables imaging and therapeutic radioiodine treatment, significantly reducing tumor growth in a mouse model.

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Area of Science:

  • Oncology
  • Gene Therapy
  • Medical Imaging
  • Nanomedicine

Background:

  • The sodium iodide symporter (SLC5A5/NIS) functions as a theranostic gene, enabling both non-invasive imaging of gene expression and targeted radioiodine therapy.
  • Genetically engineered mesenchymal stem cells (MSCs) possess inherent tumor-homing capabilities, making them promising vehicles for delivering therapeutic genes like NIS to non-thyroidal tumors.
  • Pancreatic ductal adenocarcinoma (PDAC) remains a challenging malignancy with limited effective therapeutic options, necessitating novel treatment strategies.

Purpose of the Study:

  • To evaluate the tumor specificity and therapeutic efficacy of MSCs engineered to express the sodium iodide symporter (NIS) in an advanced mouse model of pancreatic ductal adenocarcinoma (PDAC).
  • To assess the potential of NIS-mediated gene delivery by MSCs for both diagnostic imaging and therapeutic radioiodine treatment of pancreatic cancer.

Main Methods:

  • Syngeneic murine MSCs were stably transfected with a plasmid encoding the NIS gene (NIS-MSCs).
  • In vivo imaging was performed using 123I-scintigraphy and 124I-PET to detect radioiodide accumulation in PDAC tumors following systemic injection of NIS-MSCs.
  • Tumor specificity and therapeutic efficacy were assessed through immunohistochemistry (IHC) for NIS, α-SMA, and Ki67, and by monitoring tumor growth after 131I therapy cycles.

Main Results:

  • Systemic administration of NIS-MSCs led to significant, perchlorate-sensitive radioiodide accumulation in PDAC tumors, confirmed by in vivo imaging.
  • Immunohistochemistry confirmed active recruitment of NIS-MSCs into the tumor stroma, demonstrating successful targeting.
  • A therapeutic regimen involving three cycles of MSC-mediated NIS delivery followed by 131I administration significantly delayed and reduced tumor growth compared to control groups.

Conclusions:

  • Mesenchymal stem cells serve as effective vehicles for delivering the NIS theranostic gene to pancreatic tumors in an advanced endogenous PDAC mouse model.
  • MSC-mediated NIS gene delivery facilitates targeted radioiodine uptake for both imaging and therapy, showing significant therapeutic effects in reducing tumor growth.
  • These findings support the clinical potential of MSC-based NIS gene therapy for imaging-guided radioiodine treatment of pancreatic cancer.