ON-CHIP PURIFICATION OF [
18
F]FDG IN
POSITRON EMISSION TOMOGRAPHY RADIOTRACER SYNTHESIS
Mark D. Tarn
1
, Giancarlo Pascali
2
, Francesco De Leonardis
1
,
Paul Watts
1
, Piero A. Salvadori
2
and Nicole Pamme
1
1
Department of Chemistry, The University of Hull, Cottingham Road, Hull HU6 7RX, UK
2
Department of Radiopharmaceutical Chemistry, CNR Institute of Clinical Physiology, 56124 Pisa, ITALY
ABSTRACT
We demonstrate the use of microfluidic modules for purification of the Positron Emission Tomography (PET)
radiotracer, 2-deoxy-2-[
18
F]fluoro-D-glucose ([
18
F]FDG), as part of an integrated microfluidic Radiochemistry-On-Chip
(ROC) platform for complete radiotracer synthesis. Two different modules were applied to the purification of [
18
F]FDG
as synthesized by a commercial system and by initial tests of the ROC platform itself.
KEYWORDS
[
18
F]FDG, Positron Emission Tomography (PET), purification, radiochemistry, solid-phase extraction (SPE).
INTRODUCTION
Positron Emission Tomography (PET) is a molecular imaging technique involving the injection into a patient and sub-
sequent monitoring of a radioisotope (e.g. [
18
F]fluoride) labeled drug molecule (radiotracer), and is employed as a diag-
nostic tool in oncology, cardiology, and the neurosciences. Although many different radiotracers are available, the most
common is glucose labeled with [
18
F]fluoride: 2-deoxy-2-[
18
F]fluoro-D-glucose, better known as [
18
F]FDG. [
18
F]FDG, as
well as other radiotracers, is manufactured via the use of automated synthesizers housed within heavily shielded and bulky
“hot cells”. Due to the half-life of the radioisotope and the limited quantities produced by a cyclotron prior to radiotracer
manufacture, each step of the synthesis must be carried out rapidly and with high efficiency. In recent years, micro-
fluidic devices have shown great promise in the synthesis of PET radiotracers thanks to rapid synthesis times and minimal
shielding requirements [1-3]. However, most reported devices focus only on the synthesis step of the procedure or, to a
lesser extent, the radioisotope pre-concentration step prior to the synthesis, neglecting other key processes in the produc-
tion that could equally benefit from miniaturization. In particular, on-chip purification of the final radiotracers has not
been explored, instead being achieved off-line via conventional solid-phase extraction (SPE) cartridges with large dead
volumes. As part of a European Union FP7 project and in collaboration with Siemens, we have been developing a “Radio
chemistry-On-Chip” (ROC) platform that incorporates all aspects of the synthetic procedure into a modular microfluidic
platform. Previously, we presented a module for the pre-concentration of [
18
F]fluoride from irradiated water for subse-
quent radiotracer synthesis [4,5]. Here, we extend this technique further and demonstrate microfluidic modules for the pu-
rification of [
18
F]FDG, synthesized by (i) a commercial Advion NanoTek system utilizing a capillary-based microreactor,
and (ii) initial tests of the ROC platform itself.
Figure 1: (a) Schematic of the chip design, consisting of a bottom plate etched to a depth of 250 m, and a top plate
etched to 50 m. When bonded, they formed a 300 m deep chamber with a shallow triangular section acting as a dam
to trap particles. (b) Single module containing all four SPE particle types required for [
18
F]FDG purification. Each
chamber was filled with two of the resins, and the outlet of the upper chamber was routed into the inlet of the lower
chamber. (c) Train of purification modules, with each chamber containing only one type of particle, thereby doubling the
trapping capacity compared to the single module. The outlet of each module was connected to the inlet of the next, al-
lowing solutions to pass through each chamber consecutively.
16th International Conference on
Miniaturized Systems for Chemistry and Life Sciences
October 28 - November 1, 2012, Okinawa, Japan 978-0-9798064-5-2/μTAS 2012/$20©12CBMS-0001
1795