Extraction Paper Chromatography Technique for
the Radionuclidic Purity Evaluation of
90
Y for
Clinical Use
Usha Pandey,
†
Prem S. Dhami,
‡
Poonam Jagesia,
‡
Meera Venkatesh,*
,†
and M. R. A. Pillai
§
Radiopharmaceuticals Division and Fuel Reprocessing Division, Bhabha Atomic Research Centre (BARC), Mumbai-400085,
India, and Industrial Applications and Chemistry Section, Division of Physical and Chemical Sciences, IAEA,
Wagramerstrasse 5, A 1400, Vienna, Austria
Yttrium-90 used for therapy should be of very high
radionuclidic (RN) purity (>99.998%) as the most prob-
able contaminant, strontium-90, is a bone seeker with a
maximum permissible body burden of 74 kBq (2 μCi)
only. None of the current known methods of RN purity
estimations is adequate to reliably measure the
90
Sr RN
impurity at such low levels. Our aim was to develop a
reliable technique to accurately determine the amount of
90
Sr in
90
Y used for therapy. This new technique combines
chelate-based extraction with paper chromatography using
paper impregnated with 2-ethylhexyl, 2-ethylhexylphos-
phonic acid (KSM-17), which is a
90
Y-specific chelator.
A PC strip impregnated with KSM-17 at the point of
spotting is used for chromatography. Upon development
with normal saline,
90
Sr moves to the solvent front leaving
90
Y completely chelated and retained at the point of
spotting. The activity at the solvent front (
90
Sr) is quanti-
fied by liquid scintillation counting, and the data are
compared with the total applied activity to provide the RN
purity of the test solution. The method has a sensitivity
of g74 kBq (2 μCi) of
90
Sr per 37 GBq (1 Ci) of
90
Y. This
novel, innovative, and simple technique offers a reliable
solution to the unanswered problem of estimation of
90
Sr
content in
90
Y used for cancer therapy.
Targeted therapy using
-
emitting radionuclides is expected
to rapidly expand in the coming years.
90
Y-based radiopharma-
ceuticals are widely used for the treatment of cancer as well as in
radiation synoviorthesis.
1-8
The increasing application of
90
Y in
nuclear medicine is due to its suitable nuclear characteristics (T
1/2
64.1 h,
-
max
2.28 MeV, no γ emission). Availability of large
quantities of high specific activity
90
Y with very high radionuclidic
(RN) purity is essential for expanding the scope of targeted
therapy using this important therapeutic radionuclide. High
specific activity
90
Y obtained from a
90
Sr/
90
Y generator system is
required for the preparation of peptide/antibody-based,
90
Y-labeled
radiopharmaceuticals used for receptor/antigen targeting in the
tumor.
9
These radiopharmaceuticals are prepared either in a
central radiopharmacy or in a hospital- based radiopharmacy using
90
Y in inorganic form, usually as the chloride or acetate, supplied
by commercial manufacturers. In order to ensure good radiop-
harmacy practice, it is mandatory to perform the radiopharma-
ceutical quality control prior to administration to the patient.
The QC test for
90
Y radiopharmaceuticals or alternatively the
radiochemical used for its preparation should include the RN
purity evaluation to confirm that the
90
Sr level is below the
permissible limit. In the case of
90
Y, such a quality control test to
estimate the RN impurity is very important, because the parent
90
Sr, which is most likely the RN impurity, has a very low
maximum permissible body burden of 74 kBq (2 µCi)
10
as it
localizes in the skeleton. In all generator-produced radionuclides,
the only potential radionuclidic contamination is the parent
radionuclide, provided the parent radionuclide used is pure.
Generally, RN purity estimation is performed by γ spectrometry
since many radionuclides used in nuclear medicine have γ
emission along with
-
emission, such as
188
W and
188
Re.
11
However, in the case of the
90
Sr/
90
Y pair, both the parent and
daughter are pure
-
emitters and no γ emissions are available
to permit γ analysis. In addition, the
-
spectra of these two
isotopes overlap to some extent. If the parent radionuclide had γ
* To whom correspondence should be addressed. E-mail: meerav@barc.gov.in.
Fax: +91-22-25505151.
†
Radiopharmaceuticals Division, Bhabha Atomic Research Centre (BARC).
‡
Fuel Reprocessing Division, Bhabha Atomic Research Centre (BARC).
§
IAEA.
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10.1021/ac701651u CCC: $40.75 © 2008 American Chemical Society Analytical Chemistry, Vol. 80, No. 3, February 1, 2008 801
Published on Web 01/04/2008