Journal of Nuclear and Radiochemical Sciences, Vol. 6, No. 3, pp. 189-191, 2005

Application of PZC to 188W/188Re Generators
H. Matsuoka,*, a K. Hashimoto,a Y. Hishinuma,b K. Ishikawa,b H. Terunuma,b K. Tatenuma,band S. Uchidac
aDepartment of Research Reactor, Japan Atomic Energy Research Institute, Tokai-mura, Ibaraki 319-1195, JapanKAKEN Co., Mito-shi, Ibaraki-ken, 310-0903, JapancTokyo Nuclear Service, Co., Tokai-mura, Ibaraki-ken, 319-1112, Japanb

Received: July 31, 2005; In Final Form: September 30, 2005
Applicability of newly developed PZC (poly zirconium compound) to an adsorbent for a 188W/188Re generator system was investigated for long term. The PZC generator gave reproducible 188Re elution yields (60–75%) with
0.03% of 188W parent breakthrough during 154 days corresponding to twice of the half-life of 188W (69.4 d).
Furthermore, the labeling yields of hydroxyethyliden diphosphonic acid and mercaptoacetyltriglycine with 188Re
eluted from the PZC column were high enough and there was no significant different with the results using 188Re
eluted from the alumina system. The 188W/188Re generator prepared by PZC indicated a good performance for thepractical use.

1. Introduction
Rhenium-188 (T1/2 = 17.0 h) is an attractive radionuclide forradiotherapy and can be obtained at carrier-free levels from β decay of the long-lived 188W (69.4 d) produced by the double neutron capture of 186W in a reactor.1, 2 The 188W/188Re generators areof particular interest,3 since 188Re can be produced repeatedly at alow cost during a long period for the synthesis of labeled compounds. However, the relatively large volume of 0.9% NaCl arerequired for the elution of 188Re from traditional alumina-based188
W/188Re generators because the parent 188W is produced in a
relatively low specific activity by the double neutron capture
reaction of 186W with the low cross sections. Therefore, methods
for concentration of 188Re solution from alumina-based 188W/188Re
generators have developed by a tandem cation-anion column
system4 or by a single anion exchange column system.5, 6
On the other hand, newly developed poly zirconium compound (PZC) 7 as the adsorbent of 99Mo has more than 100times higher adsorption capacity of molybdenum than alumina.
PZC enables to prepare a more compact 99Mo/ 99mTc generator
than alumina. Development of compact 99Mo/ 99mTc generators
by using PZC has been progressed in the project of FNCA
(Forum for Nuclear Cooperation in Asia).8 In this study, applicability of PZC to an adsorbent for a 188W/188Re generator system- the adsorption behavior of 188W was investigated for longterm (about 5 months). Labeling yields of hydroxyethylidene
diphosphonic acid (HEDP) and mercaptoacetyltriglycine(MAG3) with 188Re obtained from the PZC-based generators
were compared with those with 188Re obtained from aluminabased generators.
2. Experimental
PZC was synthesized through the thermal condensation
reaction between ZrCl4 and isopropyl alcohol (PrOH) according to the procedure of Tanase et al.7 Two different lots of PZC
which have 483 and 526 mg W/g PZC of the maximum adsorption capacity of W were used in this study.
2.1. Production of 188W.2 Tungusten-188 was produced by
the double neutron capture reaction of 186W. The target material

was 99.79% enriched 186WO3 (ISOTEC Inc., USA or Euriso-top,France). The target (25–50 mg) in a quartz ampoule was irradiated for 26–52 days in JMTR (thermal neutron flux, 2.7 × 1014
cm−2·s−1). The irradiated target was allowed to stand for morethan 4 weeks for decay of 187W (23.72 h). The irradiated target
was dissolved in 2 M NaOH with heating. The specific activityof 188W was 5∼13 MBq/mgWO3 at the end of bombardment.
2.2. Preparation of 188W/188Re generators by using PZC.
Preparation of 188W/188Re generators based on PZC was shownin the Scheme 1. Na2WO4·2H2O which corresponds to the maximum adsorption capacity of W to 1 g of PZC, PZC and the 188Wsolution (1.3 – 4.1 MBq) were added and pH was adjusted toabout 7 with 0.1 M HCl. The solution was heated to 90 ˚C for 3
hours with occasional stirring. After eliminating the fine powdered PZC by decantation, the PZC adsorbed 188W was packed
to a glass column. The PZC column (8 mmφ × 24–32 mm) was
then washed with normal saline. Rhenium-188 was eluted withnormal saline after the radioequilibrium between 188W and 188Re
had almost reached. The radioactivity of 188Re was determinedby γ -ray spectroscopy using a calibrated HPGe detector.
Na2WO4 • 2H2O, 557 mgW/14.0 mL ( pH 8.4 )PZC 1 g (Lot#020315)
188

W soln., 0.1 mL ( 1.34 MBq )Adjustment of pH ( 0.1 M HCl )Column-A

Column-B

pH 7.10pH 7.23

Heating & Stirring ( 90 ºC, 3 h )Decantation

Column Packing

Washing with 0.9% NaCl

*Corresponding author. E-mail: matsuoka.hiromitsu@jaea.
go.jp. FAX: +81-29-282-5932.

Scheme 1. Preparation of 188W/188Re generators based on PZC.

© 2005 The Japan Society of Nuclear and Radiochemical Sciences
Published on Web 12/28/2005

190 J. Nucl. Radiochem. Sci., Vol. 6, No. 3, 2005

Matsuoka

188

The W/ Re alumina generator was prepared as describedin the literature.3
2.3. Preparation of 188Re-HEDP and 188Re-MAG3. 188ReHEDP 9: HEDP was purchased from Kishida Chemical Co.,
Japan. To an HEDP aqueous solution (35.8 mg/280 µL), distilled water (504 µL), l-ascorbic acid (4.56 mg), 1 M HCl (336µL), 400 µL of a 188Re solution from the generators (PZC andalumina), and 120 µL of a stannous chloride solution (3.80 mg/mL of SnCl 2 · 2H 2O/0.6 M HCl) were added. The reaction
mixture was allowed to react in boiling water for 30 min. The
final pH of the reaction mixture was 0.7. Radiochemical yieldof 188Re-HEDP was determined silica gel TLC (Merck No.
5735/acetone) and paper chromatography (Whatman No.
1/0.9% NaCl). The distribution of 188Re in TLC and PC wasmeasured with a radioanalytic imaging system (AMBIS-100).
188Re-MAG310 : To 0.55 mg of S-Bz-MAG3, 450 µL of 0.1 M
HCl and 450 µL of a freshly prepared SnCl 2 ·2H 2O in 0.1 M
citrate-buffer (pH = 5) (6 mg / mL of SnCl2 ·2H2O) were added.
The reaction mixture was vigorously stirred by ultrasonicwaves and 300 µL of a 188Re solution from the generators wasadded. After stirring the solution by vortex, the mixture in aclosed vial was allowed to react in boiling water for 30 min.
The mixture was cooled on ice for 5–10 min. The final pH of
the reaction mixture was 2.4. After the solution was filteredthrough a 0.22 µm filter, radiochemical yields of 188Re-MAG3
were determined by HPLC (Hypersil BDS-5C18, 4.6 × 150mm, Chemco Science Co., Japan) using 4% EtOH - 0.01 M
phosphate buffer (pH = 7) at 1 mL/min of a flow rate. The liquid chromatograph used was a Waters 2690 separations module
equipped with a Waters 996 photodiode array detector and aradio-HPLC detector (Packard Radiomatic 515TR).
3. Results and Discussion
3.1. Adsorption yield of 188W to the PZC column. After an
non-adsorbed 188W was removed by the decantation and washing the column with 0.9% NaCl, adsorption yield of 188W to thePZC column was determined. Adsorption yield of 188W to PZC
was 70–95% and was almost the same as that of 99Mo.840
3020108060

40: column A: column B

200020

40

50

60

80

100

120140Elapsed time / dFigure 2. Elution yield of 188Re.
60

2nd Miking
After 40 days

4030201050

3rd Miking
After 75 days

4030
201000 2 4 6 8 10 12 14 16 18 2000 2 4 6 8 10 12 14 16 18 2000 2 4 6 8 10 12 14 16 18 20

Elution volume / mL

Elution volume / mL

Elution volume / mL

403020105060

5th Miking
After 154 days

40302010

Elution of 188Re / %5060

4th Miking
After 112 days

Elution of 188Re / %60

Elution of 188Re / %100

Elution of 188Re / %50

3.2. Elution behavior of Re from the PZC generator.
Elution profile of 188Re from the PZC generator with 0.9% NaClsolution was investigated 12 days to 154 days after the column
preparation, as shown in Figure 1. More than 90% of 188Re waseluted from the PZC generator in the first 4 mL of the effluents,
however no 188Re was eluted from the alumina-based generator
in the first few milliliters (the volume depends on column size).
It is due to the fact that 188W distributed uniformly in the PZC
column whereas 188W adsorbed on the top of alumina column.
Furthermore, the elution profile was reproducible for 154 days
after the column preparation. The flow rate of generators wasinfluenced by the conditions of column preparation and was different ranging from 0.4 to 2.4 mL/min. However, the differenceof the flow rate of generators in this range did not influence theelution profile of 188Re.
Figure 2 shows the elution yields of 188Re from the PZC generators. Though the elution yield of 188Re decreased graduallyfrom 75% with increasing elapsed time, it was 56–60% evenafter 154 days. Decrease of the elution yield with increasing60

1st Miking
After 12 days

Elution of 188Re / %Elution of 188Re / %

60

188

Elution yield of 188Re / %188

50Alumina column

4030201000 2 4 6 8 10 12 14 16 18 2000 2 4 6 8 10 12 14 16 18 2000 2 4 6 8 10 12 14 16 18 20

Elution volume / mL

Elution volume / mL

Elution volume / mLFigure 1. Elution behavior of 188Re from the PZC generator (PZC column: 8 mmφ × 32 mm, alumina column: 10 mmφ × 60 mm).

160

J. Nucl. Radiochem. Sci., Vol. 6, No. 3, 2005 191

Application of PZC to 188W/188Re Generators
9999m

7

elapsed time was also observed for Mo/ Tc PZC generators.
And, the same phenomenon was also observed for the alumina
based 188W/188Re generator systems.5, 11 The elution yield of 188Re
from the alumina generator decreased gradually from 80% to64% within 3 months.53.3. Breakthrough of 188W. Breakthrough of 188W wasdefined as the ratio of 188W radioactivity to 188Re radioactivity inthe 188Re effluents. The radioactivity of 188W in the 188Re effluent at the 3rd milking (27 days after the column preparation)
was determined by extrapolation of the radioactivity of thedaughter 188Re after decaying the initial 188Re, as shown inFigure 3. The breakthrough of 188W was 0.03% and two times
higher than 99Mo breakthrough of Radiopharmaceuticals Low
Limit of Japan (0.015%). However, the 188W breakthrough canbe reduced by using an alumina column as the second column.12
3.4. Labeling of HEDP and MAG3 with 188Re. Labelingof HEDP and MAG3 with 188Re eluted from the PZC generator
and the alumina-based generator was investigated. The labeling yield of 188Re-HEDP and 188Re-MAG3 was more than 90%,respectively. There are no significant different in the labelingyield of 188Re-HEDP and 188Re-MAG3 prepared with different
188
Re source.
Peak area of 155 keV gamma ray / cps

10000

1000

100

1010.1
0400

800

1200

Elapsed time / hFigure 3. Determination of 188W breakthrough in the 188Re effluent.

4. Conclusion
The adsorption yield of 188W to PZC was 70 – 95%. Morethan 90% of 188Re was eluted in the first 4 mL. The 188Re elution yields were 60 – 75% during 154 days corresponding totwice of the half-life of 188W (69.4 d). The parent 188W breakthrough was 0.03% by measuring γ -rays of the daughter 188Re.
And, the labeling yields of HEDP and MAG3 with 188Re eluted
from the PZC column were high enough and equal to theresults using 188 Re eluted from the alumina system. The188
W/188Re PZC generator prepared with a low radioactivity (afew MBq) of 188W indicated a good performance for the practical use. However, further investigation on various kinds ofcharacteristics which might be affected by higher radioactivityof 188W is needed.
References(1) F. F. Knapp Jr., A. P. Callahan, A. L. Beets, S. Mirzadeh,and B.-T. Hsieh, Appl. Radiat. Isot. 45, 1123 (1994).
(2) K. Kobayashi, S. Motoishi, K. Terunuma, A. A. Rauf, andK. Hashimoto, Radiochmistry 42, 551 (2000).
(3) A. P. Callahan, D. E. Rice, and F. F. Knapp, Jr., NucCompact
20, 3 (1989).
(4) S. Guhlke, A. L. Beets, K. Oetjen, S. Mirzadeh, H.-J.
Biersack, and F. F. Knapp Jr., J. Nucl. Med. 41, 1271 (2000).
(5) H. Kamioki, S. Mirzadeh, R. M. Lambrecht, R. Knapp, Jr.,and K. Dadachova, Radiochim. Acta 65, 39 (1994).
(6) A. Mushtaq, Nucl. Med. Commun. 25, 957 (2004).
(7) M. Tanase, K. Tatenuma, K. Ishikawa, K. Kurosawa, M.
Nishino, and Y. Hasegawa, Appl. Radiat. Isot. 48, 607 (1997).
(8) Proceedings of the FNCA 2003 Workshop on the Utilization of Research Reactors, January 12–16, 2004, Jakarta–Serpong, Indonesia.
(9) K. Hashimoto, Appl. Radiat. Isot. 49, 351 (1998).
(10) S. Guhlke, A. Schaffland, P. O. Zamora, J. Sartor, D.
Diekmann, H. Bender, F. F. Knapp, and H.-J. Biersack, Nucl.
Med. Biol. 25, 621 (1998).
(11) B.-T. Hsieh, A. P. Callahan, A. L. Beets, G. Ting, and F. F.
Knapp Jr., Appl. Radiat. Isot. 47, 23 (1996).
(12) A. P. Callahan, D. E. Rice, D. W. Mcpherson, S. Mirzadeh,and F. F. kanpp Jr., Appl. Radiat. Isot. 43, 801 (1992).