Synthesis of 18F chlorofluorocholine, a new pet developer

The development of 18F chlorofluorocholine in specific areas improves the diagnosis rate of bladder cancer, for example. This paper introduces the synthesis and application fields of 18F chlorofluorocholine pet development reagent. At the same time, fluorocholine and OTS chlorofluorocholine were synthesized by Fluorio pharmaceutical as the standard reference materials of 18F, providing reference samples for the development of 18F.

SyNTheSIS Of [18f]flUOROmeThylChOlINe ([18f]fCh)   

vIa [18f]flUOROmeThyl TOSylaTe

Melissa E. Rodnick, Allen F. Brooks, Brian G. Hockley,  
Bradford D. Henderson, and Peter J. H. Scott
Department of Radiology, University of Michigan School of Medicine,  
Ann Arbor, Michigan, USA

1  INTRODUCTION

Prostate cancer therapy ranges from curative therapy for localized prostate cancer 
to life‐prolonging treatment and palliation for in the case of disseminated prostate 
cancer [1]. Accurate staging of prostate cancer is essential to in selecting the most 
appropriate treatment for a given patient. This has created an urgent need for accu-
rate and noninvasive methods for staging of prostate cancer [2], and [18F]fluoro-
methylcholine‐PET is one such method. Primary prostate cancer cells, along with 
its metastases, are known to upregulate choline kinase, which, in turn, leads to an 
elevated uptake of choline for the biosynthesis of phospholipids. Intracellular 
phosphorylation traps choline inside the cell, and therefore, PET imaging with 
[18F]fluoromethylcholine can readily detect this trapping, and differentiate prostate 
cancer cells from neighboring nonmalignant tissue [3–5].

SynTHESIS oF [18F]FluoRoMETHylCHolInE ([18F]FCH)

Historically, [18F]fluoromethylcholine has been prepared by fluoromethylation of dimethylaminoethanol (DMAE) with [18F]fluorobromomethane [3–10]. However, we have only obtained low yields of product with this method in our laboratory because of compatibility issues between gaseous [18F]fluorobromometh-ane and the liquid phase synthesis modules we employ for most routine radiosyntheses of fluorine‐18‐labeled radiotracers. We therefore desired a liquid‐phase method of preparing [18F]fluoromethylcholine that is complementary to the gas‐phase method reported in Volume 1 of this series [7], so that radiochemists can select the method that is most compatible with their own synthesis equipment. We  recently developed a fully automated one‐pot liquid‐phase synthesis of [18F]  fluoromethylcholine (Fig. 1) via in situ formation of [18F]fluoromethyl tosylate [11] and present an expanded discussion of the synthesis herein.

2  SyNTheSIS PROCeDUReS
CAUtion: All radiochemical syntheses must be carried out using appropriate 
equipment in a facility authorized for the use of radioactive materials. Personal 
protective equipment must be worn, and all local radiation safety laws followed.
2.1  Production of [18f]fluoride[18o]H2o (2 ml)  [12] was loaded into the [18F]fluoride target [13] of a General Electric Medical Systems (GEMS) PETtrace cyclotron [14]. The target was bom-barded (60 μA beam for 30 min) to generate approximately 1.5 Ci (55.5 GBq) of [18F]fluoride by the 18o(p,n)18F nuclear reaction.

Detail