On-chip spectroscopy for the

18
quality control testing of F radiotracers
Mark D. Tarn, Stephen J. Archibald and Nicole Pamme
Department of Chemistry and Positron Emission Tomography Research Centre,
University of Hull, Cottingham Road, Hull, HU6 7RX, UNITED KINGDOM

We present the use of miniaturised absorbance and Raman spectroscopic techniques for performing several on-chip quality control (QC)
tests on the 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) radiotracer for positron emission tomography (PET) medical imaging. Absorbance
spectroscopy was employed for the determination of appearance/optical clarity and colourimetric pH determination, while Raman
spectroscopy is being developed for the analysis of residual solvents and for the identification of unpurified [18F]FDG. The platforms reduce
analysis times, radioactive exposure to personnel, and require minimal sample volumes, making them suitable for dose-on-demand
radiotracer synthesis.

PET imaging Quality control of [18F]FDG Microfluidic chip setup

[18F]FDG is a glucose analogue used to image
three layer glass
glucose metabolism (suitable for cancer imaging) chips

microfluidics enables “dose-on-demand” synthesis;
top layer:
requires miniaturisation of other production steps mixing of reagents

[18F]FDG must follow stringent QC testing
middle layer:
3.1 mm pathlength

bottom layer: outlet

injection of positron
chip clamped into
emitting radiotracer chip holder
(e.g. [18F]FDG)

optical fibres/Raman

positron annihilation probe aligned with
yields emission of
here, we employ on-chip spectroscopy for the pathlength channel
gamma radiation testing of three important QC parameters:

miniaturised Ocean

detection of γ rays allows construction of image

appearance: clear, colourless, free of particles Optics spectrometer
based on intensity and location of tracer

pH: must be in the range of pH 4.5 – 8.5

different tracers allow analysis for oncology,
simple setup for absorbance spectroscopy and
neurology, cardiology and inflammation
residual solvents: must be below threshold levels Raman spectroscopy in a miniaturised format

Absorbance spectroscopy pH determination: V-shaped plots and star plots

Universal
star plots of
indicator and signal intensity
sample/standards generated for
pumped into chip each pH standard
and mixed from the spectra
at wavelengths

spectra of
from 520–640 nm
coloured product
recorded
more accurate pH
determination

absorbance values than “yes/no”
of pH standards V-plot method
plotted at 551 nm

gives V-shaped plot

absorbance detection used to determine
a line is drawn
shape
pass/fail based on appearance/optical clarity across pH 4.5 and recognition

doses of [18F]FDG pumped directly into chip pH 8.5 values used to judge QC
pass/fail of

identified failed dose ([18F]FDG sample #5387);
[18F]FDG samples below the line will pass the [18F]FDG
exhibited yellow-green colour to the eye QC test, those above the line will fail. samples

Raman spectroscopy Conclusions

fingerprinting of
Absorbance-based detection employed for on-
a range of chip QC testing for appearance/optical clarity.
solvents that
can be used for
Colourimetric assay with absorbance detection
[18F]FDG used for pH determination by V-plots & star plots.
synthesis and
Raman spectroscopy being investigated for
for the cleaning residual solvent analysis; suitable for ethanol but
of synthesis further optimisation required for acetonitrile.
apparatus

Ethanol
Acetonitrile
Raman also used to identify unpurified samples.
LOD = 2410 ppm LOD = 870 ppm

Tests take only a few min and <2 µL of sample.

solvents used in [18F]FDG production must be
below threshold levels in the final injectable dose
Eliminates subjectivity of some QC tests and

Raman also used would reduce radiation exposure to technician.

most common solvents and allowed concentrations
to identify purified

Developed alongisde other tests towards an
ethanol: used for washing; max. 5000 ppm vs. unpurified
integrated microfluidic QC platform.
[18F]FDG samples
acetonitrile: used for synthesis; max. 410 ppm

unpurified sample Acknowledgements

calibration curves prepared for ethanol and exhibited increase The authors thank the Daisy Appeal (UK) (grant: DAhul0211) and the
acetonitrile using on-chip Raman spectroscopy University of Hull for financial support, and Dr Assem Allam for his generous
in background support of the project.