Radiolabeled imaging probe, multistep synthesis

S.R. Quake, H.R. Tseng, Multistep synthesis of a radiolabeled imaging probe using integrated microfluidics. Science 310 (2005) 1793-1796. 

Cheng-Lee et al. (2005) demonstrated the multistep synthesis of a radiolabeled imaging probe in a PDMS microreactor, consisting of a complex array of reaction channels, with typical dimensions of 200 pm (wide) 45 pm (deep). Employing a sequence of five steps, comprising of (1) [18F] fluoride concentration (500 /iCi), (2) solvent exchange from H20 to MeCN, (3) [18F]fluoride substitution of the D-mannose triflate 252 (324 ng), to afford the labeled probe 253 (100 °C for 30 s and 120 °C for 50 s), (4) solvent exchange from MeCN to H20, and finally, (5) acid hydrolysis of 254 at 60 °C, the authors demonstrated the synthesis of 2-[18F]-FDG 254 (Scheme 72). 

Lee CC, Sui G, Elizarov A, Shu CJ, Shin YS, Dooley AN, Huang J, Daridon A, Wyatt P, Stout D, Kolb HC, Witte ON, Satyamurthy N, Heath JR, Phelps ME, Quake SR, Tseng HR (2005) Multistep synthesis of a radiolabeled imaging probe using integrated microfluidics. Science 310 1793-1796... 

M. E. Phelps, S. R. Quake, H.-R. Tseng, Multistep Synthesis of a Radiolabeled Imaging Probe Using Integrated Microfluidics, Science 2005. 310, 1793-1796. 

Several academic partners and Siemens Medical Solutions USA Inc. (Molecular Imaging) in Culver City, USA, made the synthesis of an [18F]fluoride-radiolabeled molecular imaging probe, 2-deoxy-2-[18F]fluoro-D-glucose in an integrated microfluidic device (see Figure 5.1) [21]. Five sequential processes were made, and they are [18F]fluoride concentration, water evaporation, radiofluorination, solvent exchange and hydrolytic deprotection. The half-life of [lsF]fluorine (t1/2 = llOmin) makes rapid synthesis of doses essential. This is one of the first examples of an automated multistep synthesis in microflow fashion. 

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