Journal of Labelled Compounds and Radiopharmaceuticals
J Label Compd Radiopharm 2007; 50: 463–465.
Published online in Wiley InterScience
JLCR
Short Research Article
Integration of a microwave reactor with Synthia to provide a
fully automated radiofluorination moduley
´
NEVA LAZAROVA, FABRICE G. SIMEON, JOHN L. MUSACHIO, SHUIYU LU* and VICTOR W. PIKE
Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Building 10, Room B3C346, Bethesda, Maryland 20892-
1003, USA
Received 25 July 2006; Revised 2 November 2006; Accepted 22 November 2006
Keywords: microwaves; synthia; fluorine-18; m-fluorination; radioligand
Introduction
power control is located outside the hotcell and linked
to the cavity through a RF coaxial cable. The reaction
V-vial (1 ml, Alltech ) is equipped with a screw-on cap and
septum (Pierce, Tuf-Bond teflon/silicone) and a vent
needle that is connected to a glass vial (20 ml) to collect
the solvents and a charcoal trap to retain any volatile
break away radioactivity (Figure 1(b)). Liquid handling
is achieved using the Gilson Aspec auto-injector/
dispenser which forms part of the Synthia system.
Other operations of the radiosynthesis and purification
procedures are controlled by Visual Chemistry based
recipe.
Microwave technology has been very successfully app-
lied to enhance PET radiolabeling reactions, including
one-step nucleophilic radiofluorination reactions with
[
18F]fluoride ion, so they become faster, cleaner and
higher yielding.1-3 18F]Fluoride ion is produced as an
[
aqueous solution in a [18O]water target and must be
dried to become adequately nucleophilic.4 However,
examples of using microwave reactors for azeotropic
drying of the [18F]fluoride ions are rare, and automated
radiopharmaceutical production devices that include a
microwave reactor are virtually non-existent.5
The size of V-vial is restricted by the cavity diameter
because the curvature of the glass forms part of the
focusing mechanism that delivers microwave irradia-
We developed a fully automated radiofluorination
module by integrating the Resonance Instrument 521
microwave reactor6 with
[
18F]Fluoride ion in up to 200 ml of target
a Synthia radiosynthesis
tion.
18O]water can be processed efficiently. During drying
device.7 The microwave reactor provides efficient heat-
ing and Synthia provides an automation platform. A
process, starting with drying of [18F]fluoride ion in target
[
the optimal power input is 90 W and it is sufficient to
heat each step, 2 minutes in most cases. Heating time
and power input are controlled independently and
could be adjusted whenever it is necessary. The
optimal volume for a reaction is 300–500 ml. The PTFE
bonded silicone septum can be easily punctured for
delivery of fresh solvent and reagent yet seal effectively
so that volatile components of the reaction mixture
could be retained.
A general procedure for [18F]fluoride ion drying and
reaction under microwaves is as follows: the V-vial
containing 18F- in H218O, K2CO3/Kryptofix1 222
(K2.2.2) and CH3CN is placed in the microwave cavity.
Microwave heating at 90 W in 2 min ꢀ 3 pulses is
applied under N2 gas flow (200 ml min-1) which speeds
up the removal of azeotropic mixture of water and
acetonitrile. The heating cycle is repeated twice, and
each time fresh CH3CN (500 ml) is added. Precursor in
appropriate solvent is introduced in the V-vial and
[
18O]water followed by a nucleophilic fluorination, reac-
tion, both under microwave-enhanced conditions, was
established. The existing capability of Synthia for HPLC
separation, solid phase extraction purification and
product formulation were integrated into the process.
Results and discussion
The 521 microwave cavity is securely mounted on the
Synthia MKII Lab System (Figure 1(a)). The time and
*Correspondence to: Shuiyu Lu, Molecular Imaging Branch, National
Institute of Mental Health, National Institutes of Health, Building 10,
Room B3C346, Bethesda, Maryland 20892-1003, USA.
E-mail: shuiyu.lu@mail.nih.gov
yProceedings of the Ninth International Symposium on the Synthesis
and Applications of Isotopically Labelled Compounds, Edinburgh,
16–20 July 2006.
Copyright # 2007 John Wiley & Sons, Ltd.