Feasibility of sodium/iodide symporter gene as a new imaging reporter gene: comparison with HSV1-tk

  • Jae Hoon Shin
  • June-Key Chung
  • Joo Hyun Kang
  • Yong Jin Lee
  • Kwang Il Kim
  • Chul Woo Kim
  • Jae Min Jeong
  • Dong Soo Lee
  • Myung Chul Lee
Molecular Imaging

Abstract

Positron emission tomography (PET) imaging reporter genes, such as HSV1-tk and D2 receptor genes, make it possible to visualise gene expression non-invasively and repetitively in vivo. However, these systems require the synthesis of complicated substrates and the availability of expensive PET equipment. Expression of the sodium/iodide symporter (NIS) gene can be easily monitored with radioiodines and technetium-99m using a gamma camera. To evaluate the possibility of using NIS as an imaging reporter gene, we compared its characteristics with those of the conventional HSV1-tk gene. The CM cell line was made by transfecting the HSV1-tk gene into CT-26 (mouse colon carcinoma cell line). The CTN and CMN cell lines were then made by transfecting the NIS gene into CT-26 and CM. We measured the uptake of iodine-125 iodovinyldeoxyuridine ([125I]IVDU) and 125I to evaluate the expression of the HSV1-tk and NIS genes, respectively. Each cell line was injected into four flank sites in Balb/c mice. The biodistribution study was performed after intravenously injecting [125I]IVDU and 131I, and 131I scintigraphy was performed for the evaluation of NIS expression. In vitro studies indicated that CTN and CMN had 40- to 79-fold and 150- to 256-fold higher uptake of 125I than CT-26 and CM, respectively. Furthermore, CM and CMN showed 57- to 69-fold higher uptake of [125I]IVDU than CT-26 and CTN. NIS gene expression and 125I accumulation were found to be directly correlated (R2=0.923), as were HSV1-tk gene expression and [125I]IVDU accumulation (R2=0.956). Calculated signal per unit NIS and HSV1-tk mRNA expression was 23,240±3,755 cpm and 34,039±5,346 cpm, respectively. In vivo study indicated that CTN and CMN had 2.3- and 5.8-fold higher uptake of 131I than CT-26 and CM, and 1.8- and 3.5-fold higher uptake of [125I]IVDU than CT-26 and CTN. Scintigraphy using 131I easily visualised CTN and CMN tumours. In conclusion, the NIS gene may be viewed as an imaging reporter gene with comparable performance to the HSV1-tk gene for monitoring target gene expression.

Keywords

NIS gene HSV1-tk gene Radioiodines [125I]IVDU Imaging reporter gene 

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Jae Hoon Shin
    • 1
    • 3
    • 4
  • June-Key Chung
    • 1
    • 3
    • 4
  • Joo Hyun Kang
    • 1
    • 4
  • Yong Jin Lee
    • 1
    • 3
    • 4
  • Kwang Il Kim
    • 1
    • 3
    • 4
  • Chul Woo Kim
    • 2
  • Jae Min Jeong
    • 1
    • 4
  • Dong Soo Lee
    • 1
    • 4
  • Myung Chul Lee
    • 1
  1. 1.Department of Nuclear Medicine, Cancer Research InstituteSeoul National University College of MedicineChongno-gu, SeoulKorea
  2. 2.Department of Pathology, Cancer Research InstituteSeoul National University College of MedicineSeoulKorea
  3. 3.Department of Tumor Biology, Cancer Research InstituteSeoul National University College of MedicineSeoulKorea
  4. 4.Laboratory of Molecular Imaging and Therapy, Cancer Research InstituteSeoul National University College of MedicineSeoulKorea

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