An Improved Total Synthesis of PET HSV‐tk Gene Expression Imaging Agent 9‐[(3‐[¹⁸F]Fluoro‐1‐hydroxy‐2‐propoxy)methyl]guanine ([¹⁸F]FHPG)

Abstract

An improved total synthesis of [¹⁸F]FHPG starting from 1,3‐dibenzyloxy‐2‐propanol and guanine has been developed. [¹⁸F]FHPG was prepared by nucleophilic substitution of the appropriate precursor with [¹⁸F]KF/Kryptofix 2.2.2 followed by a quick deprotection reaction and purification with a simplified Silica Sep‐Pak solid‐phase extraction (SPE) method in 10–15% radiochemical yield, and 70 min synthesis time from end of bombardment (EOB).

Keywords:

• 9‐[(3‐[¹⁸F]Fluoro‐1‐hydroxy‐2‐propoxy)methyl]guanine ([¹⁸F]FHPG)
• Ganciclovir (GCV)
• Synthesis
• Positron emission tomography (PET)
• Herpes simplex virus thymidine kinase (HSV‐tk)
• Gene expression

Acknowledgments

This work was partially supported by the Susan G. Komen Breast Cancer Foundation grant IMG02‐1550 (to QHZ), the Indiana University American Cancer Society (ACS) Institutional Grant Committee grant IRG‐84‐002‐17 (to QHZ), the Indiana University Cores Centers of Excellence in Molecular Hematology (CCEMH) pilot and feasibility (P/F) grant (to QHZ), the Department of Defense Congressionally Directed Medical Research Programs Grant DAMD17‐03‐1‐0077 (to TAG), the NIH/NCI grant P20CA86350 (to GDH), the Indiana 21st Century Research and Technology Fund (to GDH), and the Lilly Endowment Inc. (to the Indiana Genomics Initiative (INGEN) of Indiana University).