Preparation and biological evaluation of 2-amino-6-[18F]fluoro-9-(4-hydroxy-3-hydroxy-methylbutyl) purine (6-[18F]FPCV) as a novel PET probe for imaging HSV1-tk reporter gene expression

Hancheng Cai, Duanzhi Yin, Lan Zhang, Xiaofeng Yang, Xiaoyan Xu, Weiguo Liu, Xuesheng Zheng, Hong Zhang, Jing Wang, Yuhong Xu, Dengfeng Cheng, Mingqiang Zheng, Yanjiang Han, Mingxing Wu, Yongxian Wang

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Introduction: 2-Amino-6-[18F]fluoro-9-(4-hydroxy-3-hydroxy-methylbutyl) purine (6-[18F]FPCV) was prepared via a one-step nucleophilic substitution and evaluated as a novel probe for imaging the expression of herpes simplex virus type 1 thymidine kinase (HSV1-tk) reporter gene. Methods: Log P of 6-[18F]FPCV was calculated in octanol/phosphate-buffered saline (PBS). Stability studies were performed in PBS and bovine serum albumin (BSA). Cell uptake was performed at various time points in wild-type cells and transduced cells. For in vivo studies, tumors were grown in nude mice by inoculation with C6 cells, wild type and tk positive. The radiotracer was intravenously injected to animals, and micro-PET imaging was performed. Biodistribution of 6-[18F]FPCV was performed on another group of animals at different time points. Results: Log P of 6-[18F]FPCV was -0.517. 6-[18F]FPCV was fairly stable in PBS and BSA at 6 h. The tracer uptake in C6-tk cells was 5.5-18.8 times higher than that in wild-type cells. The plasma half-life of 6-[18F]FPCV was as follows: α t1/2=1.2 min and β t1/2=73.7 min. The average ratio of tumor uptake between the transduced tumor and the wild-type tumor was 1.69 at 15 min. Conclusion: Biological evaluation showed that 6-[18F]FPCV is a potential probe for imaging HSV1-tk gene expression. However, its in vivo defluorination may limit its application in PET imaging of gene expression.

Original languageEnglish (US)
Pages (from-to)717-725
Number of pages9
JournalNuclear Medicine and Biology
Volume34
Issue number6
DOIs
StatePublished - Aug 2007

Keywords

  • 6-[F]FPCV
  • Gene expression
  • HSV1-tk
  • PET

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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