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PET imaging of HSV-tk gene expression in breast cancer with new reporter probes [¹¹C]MeOGCV and [¹¹C]MeOPCV

¹ Department of Radiology; ² Herman B Wells Center for Pediatric Research, Indiana University, Indianapolis, Indiana

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Objectives: ¹⁸F-labeled ganciclovir (GCV) and penciclovir (PCV) analogs have shown great potential as PET reporter probes to detect HSV-tk gene expression in cancers. This study was designed to develop ¹¹C-labeled GCV and PCV analogs 8-[¹¹C]methoxyganciclovir ([¹¹C]MeOGCV) and 8-[¹¹C]methoxypenciclovir ([¹¹C]MeOPCV) as new reporter probes for PET imaging of HSV-tk gene expression in breast cancer.

Methods: The precursor Ac-GCV-NMe₂ and standard MeOGCV were prepared from GCV in multiple steps. Similarly, Ac-PCV-NMe₂ and MeOPCV were prepared from PCV in multiple steps. The tracers [¹¹C]MeOGCV and [¹¹C]MeOPCV were prepared by a novel base-catalyzed ¹¹C-methoxylation reaction of the corresponding precursor with [¹¹C]CH₃OTf, followed by a quick deprotection reaction with CH₃NH₂, and isolated by SPE purification. The tumor mice were MDA-MB-231/HSV-tk cells on the right flank and MDA-MB-231/luciferase cells on the left flank. The animal PET scanner was the IndyPET-III with 1.1 mm FWHM transaxial resolution and 1.5 mm FWHM axial resolution. The initial PET dynamic studies of [¹¹C]MeOGCV and [¹¹C]MeOPCV in breast tumor mice were performed using IndyPET-III.

Results: The overall yields for Ac-GCV-NMe₂, MeOGCV, Ac-PCV-NMe₂ and MeOPCV were 47%, 30%, 53% and 12%, respectively. [¹¹C]MeOGCV and [¹¹C]MeOPCV were synthesized in 30-35% radiochemical yield, and specific radioactivity >4 Ci/µmol at EOB. The average ratios of the maximal tk-tumor/control tumor uptake were 11.5±7.1 and 22.6±11.2 for [¹¹C]MeOGCV and [¹¹C]MeOPCV, respectively, in animal PET imaging studies.

Conclusions: [¹¹C]MeOGCV and [¹¹C]MeOPCV may be new potential PET reporter probes for HSV-tk gene expression in breast cancer.

Research Support: Susan G. Komen for the Cure BCTR0504022.

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Wang, J.-Q. Articles by Zheng, Q.-H. PubMed Articles by Wang, J.-Q. Articles by Zheng, Q.-H.