Continuous-Flow Synthesis of N-Succinimidyl 4-[18F]fluorobenzoate Using a Single Microfluidic Chip.

Hiroyuki Kimura,Eiichi Ozeki,Hideo Saji,Hiroaki Nakanishi,Masahiro Ono,Ren Iwata,Kenji Tomatsu,Hidekazu Kawashima,Hidekazu Saiki,Kenji Arimitsu,Yuji Kuge,Juri G Gelovani

doi:10.1371/journal.pone.0159303

Abstract

In the field of positron emission tomography (PET) radiochemistry, compact microreactors provide reliable and reproducible synthesis methods that reduce the use of expensive precursors for radiolabeling and make effective use of the limited space in a hot cell. To develop more compact microreactors for radiosynthesis of 18F-labeled compounds required for the multistep procedure, we attempted radiosynthesis of N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB) via a three-step procedure using a microreactor. We examined individual steps for [18F]SFB using a batch reactor and microreactor and developed a new continuous-flow synthetic method with a single microfluidic chip to achieve rapid and efficient radiosynthesis of [18F]SFB. In the synthesis of [18F]SFB using this continuous-flow method, the three-step reaction was successfully completed within 6.5 min and the radiochemical yield was 64 ± 2% (n = 5). In addition, it was shown that the quality of [18F]SFB synthesized on this method was equal to that synthesized by conventional methods using a batch reactor in the radiolabeling of bovine serum albumin with [18F]SFB.

Highlights

Positron emission tomography (PET) [1] is a powerful non-invasive imaging technology for investigating physiological parameters in living human and animal whole bodies using molecular probes labeled with PET radioisotopes
To apply the three-step reaction of [18F]SFB to a continuous-flow synthetic method using a single microfluidic chip, we initially examined 18F-fluorination, which is the first step of radiosynthesis of [18F]SFB (Fig 2)
A solution of 1 in dimethyl sulfoxide (DMSO) was run into inlet A, and a mixture of [18F]KF and Kryptofix 2.2.2 in DMSO was run into inlet B on the designed microfluidic chip pre-heated at 120°C (Fig 6a)

Summary

Introduction

Positron emission tomography (PET) [1] is a powerful non-invasive imaging technology for investigating physiological parameters in living human and animal whole bodies using molecular probes labeled with PET radioisotopes. The development and preparation of such radiolabeled molecules is a major synthetic challenge because of the short half-lives of positronemitting radionuclides such as 18F, 11C, 13N, and 15O.

Methods

Results

Conclusion