JAEA-Review-2010-065.pdf:15.99MB - 日本原子力研究開発機構

3-53
Production of No-carrier-added Lu-177 for
Radioimmunotherapy
Sa. Watanabe a) , K. Hashimoto a) , H. Hanaoka b) , K. Endo b) and N. S. Ishioka a)
a) Radiation-Applied Biology Division, QuBS, JAEA,
b) Graduate School of Medicine, Gunma University
Lutetium-177 is considered to have potential for
application in radioimmunotherapy, because it emits
-particles (E ,max=498 keV) suitable to penetrate small
tumors and its physical half-life of 6.734 days is long
enough for 177 Lu-labeled antibodies to accumulate to tumor
sites. In addition, real time imaging of biodistribution can
be done by using the 177 Lu, because the energy of -rays
(E =113 keV and 208 keV) emitted from 177 Lu is
particularly suitable for imaging by single photon emission
computed tomography. We have succeeded in the
production of high purity no-carrier-added (nca) 177 Lu of
capable of labeling antibodies using reversed-phase ion-pair
liquid chromatography. However, in this separation, nca
177 Lu could not be completely separated from more than
2.5 mg of Yb 2O 3 target. For this reason, the radioactivity
of nca 177 Lu produced by our separation method is limited
less than GBq. Therefore, for the realization of the large
scale production, we considered the adoption of a coarse
separation between Lu and Yb by using LnResin column
before reversed-phase ion-pair liquid chromatography. In
the present paper, the maximum weight of Yb 2O 3 capable of
the separation between Lu and Yb by using LnResin column
chromatography followed by reversed-phase ion-pair liquid
chromatography was investigated.
For the production of nca 177 Lu, the 176 Yb(n, ) 177 Yb
(T 1/2=1.911 h) 177 Lu process was used. An enriched
176 Yb2O 3 target ( 176 Yb:97.6%) in a quartz ampoule was
irradiated for 7 hours at JAEA JRR-3 with a thermal neutron
flux of 1 × 10 14 ncm -2 s -1 . The weight of Yb 2O 3 target was
varied from about 2 to 15 mg. Ytterbium-175 (T 1/2=4.185
d) was also produced due to the 174 Yb content in the target,
and was used as a tracer of ytterbium. The irradiated
176 Yb2O 3 target was allowed to stand for a few days for the
decay of 177 Yb (T 1/2=1.911 h). The irradiated 176 Yb 2O 3 was
then dissolved in a mixture containing both 3 mL of 6 M
HCl and 2 mL of 30% H 2O 2 with heating. The solution
was evaporated to dryness and the residue was dissolved in a
few mL of 0.1 M HCl. The solution was loaded on a
LnResin column (Eichrom technologies, 50-100 mesh,
300 mm × 8 mm ). Elution was done with 1000 mL of
2 M HCl, 30 mL of 3 M HCl and 150 mL of 6 M HCl.
Ytterbium is mainly eluted in 2 M and 3M HCl and Lu is in
3 M and 6 M HCl. The effluent was taken as three fractions
of 2 M, 3 M and 6 M HCl and the radioactivity of each
fraction was measured with a calibrated HPGe detector.
The results of elution of the LnResin column were shown
in Table 1. In 2.0, 5.7 and 10.3 mg of Yb 2O 3 targets loaded
on the LnResin column, the weight of Yb 2O 3 in 3 M and
6 M HCl fraction was less than 2 mg. On the other hand,
JAEA-Review 2010-065
- 109 -
in 15.0 mg of Yb2O 3 target, the weight of Yb 2O 3 in 3 M and
6 M HCl fraction was more than 5 mg. Since, in the
reversed-phase ion-pair liquid chromatography, nca 177 Lu
could not be completely separated from more than 2.5 mg of
Yb2O 3 target, the 15 mg of Yb 2O 3 target is too much.
Therefore about 10 mg of Yb 2O 3 target was considered to be
maximum weight of Yb2O 3 capable of the separation
between Lu and Yb by using LnResin column followed by
reversed-phase ion-pair liquid chromatography.
By irradiation of 10 mg of Yb 2O 3 for 10 days at JRR-3
with a thermal neutron flux of 1 × 10 14 ncm -2 s -1 , 3.6 GBq of
177 Lu can be produced as calculated value. Therefore, a
large scale production of 177 Lu (GBq order) for the clinical
application can be theoretically achieved. For future plan,
a large scale production of 177 Lu will be carried out by the
combination of the coarse separation by using LnResin
column and the fine separation by using reversed-phase
ion-pair liquid chromatography.
Acknowledgments
A part of this study is the result of “Development of
RI-DDS for advanced cancer diagnosis and therapy” carried
out under the Strategic Promotion Program for Basic
Nuclear Research by the Ministry of Education, Culture,
Sports, Science and Technology of Japan.
Table 1 Distribution of 175 Yb and 177 Lu in 3 M and 6 M
HCl fraction by LnResin column chromatography.
The First column shows the weight of Yb 2O 3 target
loaded on the LnResin column. The second column
shows the percentage of 175 Yb in 3 M and 6 M HCl
fraction in which lutetium is mainly eluted. The third
column shows the weight of Yb 2O 3 in 3 M and 6 M
HCl fraction, which was calculated by multiplication
of weight of Yb 2O 3 target loaded on the LnResin
column (first column) by the percentage of 175 Yb in
3 M and 6 M HCl fraction (second column). The
forth column shows the percentage of 177 Lu in 3 M and
6 M HCl fraction. In all weight of Yb2O 3, the
percentage of 177 Lu is more than 90%.
Loaded
Yb 2O 3
weight
(mg)
175 Yb in 3
M and 6 M
HCl fraction
(%)
Yb 2O 3
weight in 3
M and 6 M
HCl fraction
(mg)
177 Lu in 3 M
and 6 M
HCl fraction
(%)
2.0 11.3 0.23 91.5
5.7 11.4 0.65 96.2
10.3 16.4 1.7 96.0
15.0 35.2 5.3 90.3