ROUTINE PRODUCTION OF COPPER-64 ON 18MEV CYCLOTRON: TARGET
FABRICATION, TARGET PURIFICATION AND QUALITY CONTROL FOR ‘PROOF
OF CONCEPT’ MICRO-PET/CT
JEFFERY, C.M.1,2,3, SMITH, S.V.3,4, ASAD, A.H.1,3,5, CHAN, S.1, HARRIS, M.6, MARDON, K.7, PRICE, R.I.1,2,¶
1
Sir Charles Gairdner Hospital, Nedlands, WA, Aus. 2University of Western Australia, Nedlands, WA, Aus. 3Centre
of Excellence in Antimatter Matter Studies (CAMS), Australian National University, Canberra, ACT, Aus.
4
Brookhaven National Laboratory, Upton, NY, USA. 5Curtin University of Technology, Bentley, WA, Aus. 6Clarity
Pharmaceuticals, Aus. 7Centre for Advanced Imaging, University of Queensland, St Lucia, Qld, Aus.
¶
Corresponding author email address: charmaine.jeffery@health.wa.gov.au
change in metals contaminates nor in
yield.
64
Cu production
Cu-64 complexation with DiamSar
120%
100%
% Cu Complexed
Introduction: Copper-64 has ideal physical characteristics for PET imaging with a number of target
agents (eg. Peptides, proteins and nanomaterials) (T1/2
= 12.7 hours, β+avg= 278keV, β+max= 652.9keV,
17.87%). The aim of this work is to develop a costeffective and reproducible process for the production of
high purity 64Cu, at sufficient quantities for research
purposes and ultimately clinical use.
Material and methods: Enriched 64Ni (95%) was
electroplated onto an Au foil (as 64NiSO4 solution, with
(NH4)2SO4 added as a pH buffer, using single- or multifoil electroplating device). The 64Ni target was placed
in a custom-built solid target assembly, positioned
external to the cyclotron. The target was bombarded
with 11.6MeV protons (degraded using a custom built
graphite degrader) at a current ranging from 15-40µA,
for up to 120 minutes. A novel anion exchange separation process using organic solvent mixtures and AG1X8 resin was developed to separate 64Cu from the target material and contaminating radionuclides (eg. 55Co
and 57Co). The 64Cu product was assayed for radionuclidic and chemical purity using gamma spectroscopy
and ICP-AES/MS respectively. The specific activity of
of the 64Cu determined by ICP-MS was compared with
that obtained by titrating with varying concentrations
of DiamSar and analyzing 64Cu complexed by TLC.
ICP-MS requires the 64Cu sample decay prior to analysis, while the latter method can be conducted directly
after production, providing ‘real-time’ specific activity
data. Current research applications involve development of 64Cu-SarAr-labelled and nanoparticles for
application in future pre-clinical PET/CT imaging.
Results: Nineteen targets (with 13.89 – 29.35mg
64
Ni) were irradiated between July 2011 to March 2012.
Up to 1.2GBq of 64Cu was successfully purified from
each target using an anion exchange resin. The 64Cu
batches (at approx. 10000GBq/mL) had a specific
activity ranging from 25 to 57TBq/µmol. The radionuclidic and chemical purity were high (>98%) with
<20ppm of contaminating metal ions (i.e. Al, Fe and
Pb) in each batch. The production yield varied between
5.5 to 21.3 MBq/uA.hr. The 64Ni was recycled (up to
three times) and re-irradiated, with no evidence of
80%
60%
40%
20%
0%
1.E-08 1.E-07 1.E-06 1.E-05 1.E-04 1.E-03 1.E-02 1.E-01 1.E+00
Mass DiamSar (mg)
64
Figure 1: Per cent of Cu complexed with DiamSar
(using fixed volumes of 64Cu and DiamSar, with varying concentrations of DiamSar in solution), to calculate
the specific activity of 64Cu)
Conclusions: The radiopharmaceutical production
team at SCGH has in place a reliable and cost-effective
process for the production and transport of 64Cu. Up to
1GBq can be isolated after irradiation of an enriched
64
Ni target at 40µA for 70 minutes. The specific activity of the 64Cu ranged from 25 to 57TBq/µmol.
Acknowledgments, disclosures and funding: An
Australian Institute of Nuclear Science and Engineering grant was awarded in 2010. The Australian Nuclear Science and Technology Organisation have provided funding for equipment to support solid target research at Sir Charles Gairdner Hospital. Funding for
travel has been obtained from SCGH and the University of Western Australia.