SPECT imaging of herpes simplex virus type1 thymidine kinase gene expression by [(123)I]FIAU(1).

Abstract

RATIONALE AND OBJECTIVES:

Introduction of suicide genes, such as herpes simplex virus type1 thymidine kinase (HSV1-tk), in tumor cells has provided a useful method for tumor gene therapy. Several L-nucleosides, such as Lamivudine (3TC) and Clevudine (L-FMAU), have been successfully tested as high-potency antiviral agents. To investigate the potential differences between D- and L-isomers of nucleosides, [(125/123)I]-2'-fluoro-2'-deoxy-1beta-D/L-arabino-furanosy-5-iodo-uracil (D/L-FIAU) have been synthesized and evaluated as potential SPECT agents for imaging HSV1-tk gene expression.

MATERIALS AND METHODS:

[(125/123)I]D- and L-FIAU were prepared by iododestannylation of the respective tin precursors with (125/123)I-sodium iodide. In vitro cell uptake studies were performed by incubation of [(125)I]D- and L-FIAU in RG2 cells expressing HSV1-tk (RG2TK+). In vivo studies including biodistribution and SPECT were performed in RG2TK+ and RG2TK- tumor-bearing nude mice using [(123)I]D- and L-FIAU.

RESULTS:

Cell uptake and biodistribution studies indicated that [(125/123)I]L-FIAU did not show any high accumulation (sensitivity) or uptake ratios (selectivity) in HSV1-TK-positive (RG2TK+) tumors as compared to control tumors. In contrast, [(125/123)I]D-FIAU displayed both sensitivity and selectivity to RG2TK+ tumors. The selective in vivo accumulation of [(123)I]D-FIAU increased with time and the tumor uptake ratios (RG2TK+/RG2TK-) for 2, 4, and 24 hours averaged 6.2, 22.7, and 58.8, respectively. High-resolution SPECT of four nude tumor-bearing mice demonstrated a very high uptake of [(123)I]D-FIAU in the RG2TK+ tumor, while no significant tracer accumulation was observed in the RG2TK- tumor and other organs.

CONCLUSION:

The data suggest that only the D-isomer of [(123)I]FIAU is useful for imaging HSV1-tk gene expression in mice by high-resolution SPECT imaging.

• Authors: Seok Rye Choi, Zhi-Ping Zhuang, Ann-Marie Chacko, Paul D Acton, Juri Tjuvajev-Gelovani, Mikhai Doubrovin, David C K Chu, Hank F Kung
• Journal: Academic radiology (Acad Radiol) Vol. 12 Issue 7 Pg. 798-805 (Jul 2005) ISSN: 1076-6332 [Print] United States
• PMID: 16039533 (Publication Type: Journal Article)

Chemical References

• Iodine Radioisotopes
• Nucleosides
• Radiopharmaceuticals
• Arabinofuranosyluracil
• Thymidine Kinase

Topics

• Animals
• Arabinofuranosyluracil (analogs & derivatives)
• Gene Expression
• Genetic Therapy
• Glioma (diagnostic imaging, enzymology)
• Iodine Radioisotopes
• Male
• Mice
• Mice, Nude
• Nucleosides
• Radiopharmaceuticals
• Rats
• Simplexvirus (enzymology)
• Thymidine Kinase (genetics)
• Tomography, Emission-Computed, Single-Photon