Short Communication
IMPACT OF PROLONGED REDUCED-PRESSURE CONDITION PRIOR TO PRECURSOR LABELING
ON THE LABELING EFFICIENCY OF F-18 FLUOROCHOLINE SYNTHESIS
HISHAR H.
*
, HANAFI M. H., FATHINUL FIKRI A. S.
1
Centre for Diagnostic Nuclear Imaging, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
Email: hishar.hassan@gmail.com
Received: 12 Oct 2017 Revised and Accepted: 24 Feb 2018
ABSTRACT
Objective: The goal of this preliminary work was to observe the impact of the prolonged reduced-pressure condition prior to labeling stage on the
F-18 Fluorocholine labeling yield at the end of synthesis.
Methods: At this present work, the condition inside the reactor vial prior to labeling stage was manipulated. In the first technique of syntheses of F-
18 Fluorocholine, the condition inside the reactor vial was set at 0 atmospheric pressure (0 atm) while in the second technique the condition inside
the reactor was set at reduced-pressure (between-0.65 to-0.85 bars) with the delay time of 120 seconds. At the end of the synthesis, the impact of
the prolonged reduced-pressure condition prior to precursor labeling was measured in terms of labeling yield of F-18 Fluorocholine.
Results: With the second technique, the labeling yield of F-18 Fluorocholine was elevated from 9.7% (the first technique) to 24.3%.
Conclusion: This preliminary work indicates that delay in a reduced-pressure condition prior to labeling step has greatly improved the labeling
yield of F-18 Fluorocholine at the end of synthesis. Using this approach, the labeling yield of F-18 Fluorocholine was elevated from 7.5% to 24.3%.
Keywords: Azeotropic drying, F-18 Fluorocholine, Labeling yield, Reduced-pressure
© 2018 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
DOI: http://dx.doi.org/10.22159/ijpps.2018v10i4.23057
N-methyl-(C-11) choline (C-11 choline) was the first choline derivative
labeled with positron emitter isotopes [1]. Since then, C-11 choline
proved to be an effective marker in various tumors located in brain,
lungs, urinary bladder, and most significantly in prostate [1-5]. However,
due to the short half-life of radioisotope carbon-11 compared to
radioisotope fluorine-18, it becomes a limiting factor to those centres
which are not cyclotron-bounded. For this reason, fluorinated labeled
choline, N,N-dimethyl-N-(F-18)-fluoromethyl-2-hydroxyethyl ammonium
or known as F-18 Fluorocholine, has been developed as a substitute for
choline derivatives in Positron Emission Tomography (PET) imaging
technique [6-8]. Due to its high positron emission abundance, low
positron energy, the small ion radius and its ease of production, fluorine-
18 (F-18) become the most extensively used radioisotope for PET
imaging technique. In addition, the half-life of fluorine-18 is relatively
long enough to allow for multistep synthesis and transportation to
remote hospitals without an on-site cyclotron [9-10].
In 2001, DeGrado had successfully synthesised F-18 Fluorocholine
using the reactive intermediate, F-18 fluorobromomethane (F-18
CH2Br) [11-13]. DeGrado’s work was followed by Iwata in 2002
but using F-18 fluoromethyl triflate, a different reactive
intermediate [14]. In 2008, Kryza and co-workers had successfully
synthesised F-18 Fluorocholine using a similar approach as
DeGrado but eliminated the use of semi-preparative HPLC column
for purification [15].
In this attempt, F-18 Fluorocholine were synthesised in accordance
with Kryza method on an automated synthesis platform, GE
TracerLab MXFDG [15]. It is known the limiting factor that affects the
F-18 Fluorocholine production around the globe, is due to its
relatively low yield. Therefore, this preliminary works attempt to
investigate whether a prolonged reduced-pressure condition prior
to labeling step will affect the yield of F-18 Fluorocholine.
Fig. 1: Synthesis of F-18 fluorocholine
At the present works, two techniques were employed to observe
the impact of the prolonged reduced-pressure condition on the
yield of F-18 Fluorocholine. In the first technique, during the
syntheses of F-18 Fluorocholine (n = 3), succeeding to F-18 ions
elution to reactor vial, the condition inside the reactor was set at 0
atmospheric pressure (0 atm). Meanwhile, in the second
International Journal of Pharmacy and Pharmaceutical Sciences
ISSN- 0975-1491 Vol 10, Issue 4, 2018