Nucl Med Mol Imaging.  2009 Oct;43(5):478-486.

The Synthesis of the Stable IVDU Derivative for Imaging HSV-1 TK Expression

• Kim EJ
• Choi TH
• Ahn SH
• Kim BS
• Park H
• Cheon GJ
• Rhee HJ
• An GI

Abstract

PURPOSE
5-iododeoxyuridine analogues have been exclusively developed for the potential antiviral and antitumor therapeutic agents. In this study, we synthesized carbocyclic radioiododeoxyuridineanalogue (ddIVDU) and carbocyclic intermediate as efficient carbocyclic radiopharmaceuticals.
MATERIALS AND METHODS
The synthesis is LAH reduction, hetero Diels-Alder reaction as key reactions including Pd(0)-catalyzed coupling reaction together with organotin. MCA-RH7777 (MCA) and MCA-tk (HSV1-tk positive) cells were treated with various concentration of carbocyclic ddIVDU, and GCV. Cytotoxicity was measured by the MTS methods. For in vitro uptake study, MCA and MCA-tk cells were incubated with 1uCi of [(125)I]carbocyclic ddIVDU. Accumulated radioactivity was measured after various incubation times.
RESULTS
The synthesis of ddIVDU and precursor for radioiodination were achieved from cyclopentadiene in good overall yield, respectively. The radioiododemetallation for radiolabeling gave more than 80% yield with > 95% radiochemical purity. GCV was more toxic than carbocyclic ddIVDU in MCA-tk cells. Accumulation of [(125)I]carbocyclic ddIVDU was higher in MCA-tk cells than MCA cells.
CONCLUSION
Biological data reveal that ddIVDU is stable in vitro, less toxic than ganciclovir (GCV), and selective in HSV1-tk expressed cells. Thus, this new carbocyclic nucleoside, referred to in this paper as carbocyclic 2',3'-didehydro-2',3'-dideoxy-5- iodovinyluridine (carbocyclic ddIVDU), is a potential imaging probe for HSV1-tk.

Keyword

Tumor imaging; ddIVDU; carbocyclic nucleosides; Pd(0)-coupling reaction

MeSH Terms

Cycloaddition Reaction
Ganciclovir
Herpesvirus 1, Human
Idoxuridine
Radioactivity
Radiopharmaceuticals
Ganciclovir
Idoxuridine
Radiopharmaceuticals