Journal of Nuclear and Radiochemical Sciences, Vol. 2, No. 1-2, pp. 5-9, 2001

ArticlesAdsorption of 188Re Complexes with Aminomethylenephosphonate on Hydroxyapatite
Kazuyuki Hashimoto,* Hiromitsu Matsuoka, and Mishiroku Izumo
Department of Research Reactor, Japan Atomic Energy Research Institute, Tokai-mura, Ibaraki-ken 319-1195,
Japan
Received: August 23, 2001; In Final Form: November 25, 2001
The adsorption properties of newly developed 188Re complexes with aminomethylenephosphonate (amp) (EDTMPEthylenediamine-N,N,N',N'-tetrakis(methylenephosphonic acid), EDBMP - Ethylenediamine-N,N'-bis(methylenephosphonic acid) and NTMP - Nitrilotris(methylenephosphonic acid)) on hydroxyapatite was investigated.
The adsorption of 188Re complexes was strongly affected by pH and ionic strength in a solution. The adsorption
coefficient (ml/g), which is defined by the ratio of the concentration of the complex per unit weight of the hydroxyapatite to the concentration in unit volume of the solution, increased with decreasing pH and ionic strength. Theseobservations suggest that one of the causes of the adsorption of 188Re-amp is considered to be the electrostaticforces between the negative 188Re-amp complex and the positive HAP surface. The adsorption affinity of the
188
Re-amp complex for HAP increased in the order of 188Re-EDBMP<188Re-NTMP<188Re-EDTMP. Furthermore,
the adsorption coefficient of carrier-free 188Re-EDTMP was larger than that of carrier-added one under the same
conditions. From a detailed comparison of the effect of the Re carrier concentration on the adsorption coefficientof 188Re-EDTMP with its structural analysis by HPLC, we concluded that the Re carrier effect on the adsorption
coefficient was caused by the different distribution of the components in the 188Re-EDTMP mixture between the
carrier-free and the carrier-added complex.

Introduction
Rhenium-186 (186Re: T1/2, 89.24 h; Eβ, 1.07 MeV; Eγ , 137keV) and rhenium-188 (188Re: T1/2, 17.005 h; Eβ, 2.12 MeV; Eγ ,155 keV) are of current interest for therapeutic applications in
the field of nuclear medicine especially for the palliative treatment of metastatic bone pain, because of their energetic beta
particles and gamma rays suitable for imaging.1−3 Rhenium186 with a carrier can be produced in nuclear reactors,
however 188Re can be obtained at carrier-free levels from a
188
W- 188 Re generator.4 The diphosphonate ligands such as
MDP (methylenediphosphonic acid), HMDP (1-hydroxymethylene-1,1-diphosphonic acid) labeled with 99mTc have been
widely used as bone imaging agents. Preparations of 186Re and188
Re complexes with diphosphonate ligands including MDP,5, 6
HEDP (1-hydroxyethylidene-1,1-diphosphonic acid), 7−13
AEDP (1-amino-ethylenediphosphonic acid),14 APD (3-amino1-hydroxypropylidene-1,1-bisphosphonic acid)15 and ABP (4amino-1-hydroxybutylidene-1,1-bisphosphonic acid) 16 arereported and they are found to be good bone seeking agentssimilar to 99m Tc diphosphonates. Among them, the 186 ReHEDP is reported to show effective palliation of metastaticbone pain.17−22 The EDTMP, aminomethylenephosphonate
derivative, labeled with 1 5 3 Sm has also shown to be a
promising agent for effective palliative treatment of widespread skeletal metastases.23−26
In vitro studies on adsorption properties of labeled
compounds with phosphonate-containing ligands on bone havebeen limited such as 99mTc-diphosphonate,27−31 tin (117m, 119mSn)diphosphonate32 and 153Sm-EDTMP.33, 34 The adsorption studyof 186/188 Re complexes has not been so far reported. In theprevious paper, 35 we determined optimum conditions forsynthesis of 188Re complexes with aminomethylenephosphonate (EDTMP, EDBMP and NTMP) as shown in Figure 1. In
this paper, we describe the adsorption properties of the newly*Corresponding author. E-mail: hashi@popsvr.tokai.jaeri.go.jp.
FAX: +81-29-282-5932.

developed 188Re complexes with aminomethylenephosphonate
on hydroxyapatite, which is the major constituent of the hardtissues of bone. The influence of the shaking time, pH andionic strength on the adsorption was investigated from fundamental aspects. The difference in adsorption properties
between carrier-free (cf-) and carrier-added (ca-) 188 ReEDTMP was also studied.

CH2PO3H2

H2O3PCH2
NCH2CH2N
H2O3PCH2

CH2PO3H2

EDTMP

H

H
NCH2CH2N
H2O3PCH2

CH2PO3H2EDBMP

CH2PO3H2

H2O3PCH2N

CH2PO3H2

NTMP
Figure 1. Structures of the aminomethylenephosphonate ligands usedin this study.

© 2001 The Japan Society of Nuclear and Radiochemical Sciences
Published on Web 12/28/2001

6

HashimotoJ. Nucl. Radiochem. Sci., Vol. 2, No. 1-2, 2001

Experimental
Production of 188W/188Re Generator. Typically 25−35 mg
of enriched 186W as WO3 (99.79% enrichment: euriso-top) was
irradiated for 26−52 days in JAERI JMTR (a thermal neutron
flux of 2.7 × 1014 n cm−2 s−1). The 188W/188Re generator was
prepared by the alumina column system.4 The irradiated WO3
was dissolved in 2 M NaOH. The pH of a part of the 188W
solution was adjusted to about 2 using HCl. This solution wasabsorbed onto the alumina column (10 mm × 60 mm; BIORAD, AG-4, 100−200 mesh), which was conditioned with
0.01 M HCl. The column was then washed with normal saline.
Rhenium-188 was eluted with normal saline after the equilibrium between 188W and 188Re had almost been reached. The
chemical form of 188 Re obtained from the generator waschecked by paper chromatography in 0.9% saline. The chemical form of 188Re was found to be perrhenate ion (188ReO4−)
and was free from 188W breakthrough. Rhenium-188 solution(2 × 105–1 × 106 Bq ml−1) was obtained from the generator in asaline solution and was used for labeling purposes without
further purification.
Synthesis of 188Re-Aminomethylenephosphonate (188Reamp) Complex. Aminomethylenephosphonate derivatives(EDTMP, EDBMP and NTMP) were purchased from Dojindo
Laboratories, Japan. All other chemicals used were of guaranteed reagent grade.
To 0.2 M aminomethylenephosphonate aqueous solution,
distilled water, 38 mg/ml (0.216 M) l-ascorbic acid aqueous
solution, 3 M HCl for pH adjustment, a 188Re solution from thegenerator, and 38 mg/ml (0.168 M) tin(II) chloride dihydrate
solution (0.6 M HCl) were added. The final concentrations ofaminomethylenephosphonate, l-ascorbic acid and tin(II) chloride dihydrate in the reaction mixture were 0.1 M, 2.85 mg/ml
and 0.57 mg/ml. The pH of the solution was 0.8−0.9. The
final concentration of the Re varied from carrier-free levels to
20 µg Re/ml (1.074 × 10−4 M) by adding NH4ReO4 to the 188Re
solution. The reaction mixture was vigorously stirred andallowed to react in boiling water for 30 min. The formation of
188
Re-amp was checked by silica gel TLC with acetone as
described in the previous paper.35 The 188Re-amp complex was
obtained in a more than 95% yield. The distribution of 188Re in
TLC was measured with a radioanalytic imaging system(AMBIS-100).
Adsorption Studies of 188Re-amp Complex on Hydroxyapatite. Hydroxyapatite for liquid phase chromatography

was used as a adsorbent, supplied by Wako Pure Chemicals
Co. as Ca10(PO4)6(OH)2.
In a vial, 100 mg of HAP was suspended ultrasonically in 1
ml of HCl, distilled water, sodium acetate or NaOH solution
for pH adjustment and 0.5 ml of 4 M NaCl solution for ionicstrength adjustment. Then 0.5 ml of the 188Re complex solution was added. The concentration of aminomethylenephosphonate in the final solution was 2.5 × 10−2 M. The vial was
shaken mechanically in a water bath at 37˚C. At regular timeintervals, the mixture was centrifuged and an aliquot of thesolution was taken for radioactivity measurement. The
radioactivity of the 188Re complex itself in the solution wascorrected by the fraction of the 188Re complex measured bysilica gel TLC. The adsorption coefficient (ml/g), which isdefined by the ratio of the concentration of the complex per
unit weight of the hydroxyapatite to the concentration in unit
volume of the solution, was determined by measuring theradioactivity of the solution and the standard solution of 188Re.
The radioactivity of 188 Re was measured by a Cherenkovcounting method using a liquid scintillation counter (Beckman
LS3801).36
HPLC Analysis of 188Re-EDTMP. The liquid chromatograph used was a Waters 2690 separations module equippedwith a Waters 996 photodiode array detector and a radio-HPLC
detector (Packard Radiomatic 515TR). The 188Re-EDTMP wasanalyzed by reversed-phase ion-pair chromatography (Hypersil
C18 BDS-5, 4.6 mmφ × 150 mm) using a gradient systemcomprising 0.008 M tetrabutyl ammonium hydroxide (TBA) /10% methanol (pH 6.0) (solvent A) and 0.008 M TBA / 60%
methanol (pH 6.0) (solvent B). The flow rate was 1.0 ml/min
and the gradient was defined by the following points (min%B): 0-0, 5-85, 30-100.
Results and Discussion
The fractions of 188Re-EDTMP adsorbed on HAP increased
with the elapse of time and attained an almost constant value
after 24 hours within the experimental error, as shown in
Figure 2. For the adsorption isotherm experiments, a time
period of 24 h was used. In the previous paper,35 the stabilityof the carrier-free (cf-) 188Re-amp was found to be lower thanthat of the carrier-added (ca-) 188 Re-amp. However, thedecomposition of cf-188Re-EDTMP to perrhenate was scarcely
observed during the experiment, as shown in Figure 3. It was

cf-188Re-EDTMP (pH 3.5-3.6)

100

80

80
Percent yield / %Percent adsorbed / %

100

60
40
: cf-

: ca-

20
0

188

0

Re-EDTMP

188

Re-EDTMP

10
20
Shaking time / hour

30

Figure 2. Typical time variation in the adsorption of carrier-free (cf-)
and carrier-added (ca-) 188Re-EDTMP (pH 3.5, HAP 100 mg, I=1.0).

60
40: 188Re adsorbed on HAP
188: Re-EDTMP in the solution: 188ReO4- in the solution

20

0

20
10
Shaking time / hour

30

Figure 3. Chemical species during the adsorption experiment using
carrier-free 188Re-EDTMP (pH 3.5-3.6, HAP 100 mg, I=1.0).

Adsorption of 188Re Complexes with Aminomethylenephosphonate

10-8 ]

40

30

20

10

0

0.2

0.4

0.6

0.8

1

[ 10-8 ]Concentration of Re in the solution (mol/ml)

Figure 4. Adsorption isotherm of 188Re-EDTMP (Re final concentration: 1.36 × 10−11 mol/l (carrier-free; 92.5 kBq/ml) ~2.85 × 10−5 mol/l).
Correlation coefficient R=0.997.

Adsorption coefficient / (ml/g)

Adsorption coefficient / (ml/g)[

1000
cf-188Re-EDTMP

100
ca-188Re-EDTMP

10

1

3

3.5
pH

4

4.5

Figure 5. Influence of pH on the adsorption coefficient of 188ReEDTMP (HAP 100 mg, I=1.0, 24 h).

7zeta potential is positive and the positive charge on the HAPwill dominate. The pzc on HAP has been found to lie between
pH 6.4 and 8.5.37−41 Therefore, the charge of HAP in the pH
range (3 − 4.5) of the present study will be positive because thepH was lower than the pzc. Taking into consideration that the188
Re-amp complexes had negative charges analyzed by electrophoresis,35 one of the causes of the adsorption of 188Re-amp
is considered the electrostatic forces between the negative
188
Re-amp complex and the positive HAP surface.
Figure 6 showed the influence of ionic strength on theadsorption coefficient. The adsorption coefficient decreased
with increasing ionic strength. These results also show that theadsorption is mainly electrostatic. That is, it is conceivablethat the adsorption coefficient decreased due to the electrostatic shielding effect and to the competitive adsorption
between them by adding NaCl.
The comparisons of the adsorption coefficient of the 188Reamp complexes are shown in Figure 7. The adsorption coefficient increased in the order: 188 Re-EDBMP< 188 Re-NTMP<188Re-EDTMP under the same conditions. However, it isthought that the adsorption coefficients of the 188 Re-amp
complexes are also influenced by the excess aminomethylene-

1000

cf-

188

Re-EDTMP

500

ca-188Re-EDTMP

100
50

10
0

0.5
Ionic Strength1

Figure 6. Influence of ionic strength on the adsorption coefficient of
188
Re-EDTMP (pH 3.6, HAP 100 mg, 24 h).

Adsorption coefficient / (ml/g)

Concentration of Re adsorbed on HAP / (mol/g)

less than 3 −4% even after 24 hours. Furthermore, no adsorption of perrhenate to HAP was observed.
A plot of the concentration of 188Re-EDTMP in the adsorbent against that in the solution indicated a linear isotherm asshown in Figure 4. Linearity of the plot is equivalent to theconstant adsorption coefficient in the range of the complex
concentration in this experiment.
The influence of pH and ionic strength on the adsorption
coefficient was investigated. Figure 5 showed the influence ofpH on the adsorption coefficient. The adsorption coefficientincreased with decreasing pH. This result is consistent withthe adsorption behavior of 9 9 m Tc(Sn)pyrophosphate on
Ca 3 (PO 4 ) 2 . 3 1 It was observed that the adsorption of
99m
Tc(Sn)pyrophosphate at pH 4.0 was higher than at pH 7.4.
The pH influenced the charge of surface (zeta potential) of
HAP. The surface of HAP is heterogeneous, with both positive and negative charge, but with the charge density dependent on pH. When pH is higher than point of zero charge(pzc), the zeta potential is negative and the negative charge on
the HAP surface will dominate; when pH is lower than pzc, theJ. Nucl. Radiochem. Sci., Vol. 2, No. 1-2, 2001

100

50

0

ca-188Re-EDTMP

ca-188Re-NTMP

ca-188Re-EDBMP
3

3.5
pH

4

Figure 7. Comparison of the adsorption coefficient of the carrieradded (20 µg Re ml−1) 188Re-amp complex (HAP 100 mg, I=1.0, 24 h).

8HashimotoJ. Nucl. Radiochem. Sci., Vol. 2, No. 1-2, 2001

Adsorption coefficient / (ml/g)

500

400

300

200

100

0
1E-11

1E-10

1E-9

1E-8

1E-7

Concentration of Re carrier in the

188

1E-6

1E-5

1E-4

Re-EDTMP sample / (g/ml)

Figure 8. Effect of the carrier concentration on the adsorption coefficient of 188Re-EDTMP (HAP 100mg, pH 3.6, 24 h).

188

ReO4−

20 µg Re/ml

Re Radioactivity / arbit. unit

2 µg

0.2 µg0.02 µg0.002 µg

188

phosphonate in the solution. Two competitive adsorption reactions were occurred in this experiment. One is adsorption
between 188Re-amp and HAP, another is adsorption between
aminomethylenephosphonate and HAP. In order to estimate
the effect of aminomethylenephosphonate on the adsorption to
HAP, the adsorption coefficient of the 188 Re complex wasmeasured by adding further aminomethylenephosphonate solution. The adsorption coefficient of 188Re-amp decreased byadding aminomethylenephosphonate solution. The magnitudeof the decrease was in the order EDBMP≤NTMP<EDTMP,
that is, the adsorption affinity of aminomethylenephosphonate
for HAP increased in the order EDBMP≤NTMP<EDTMP.
Taking into account the order of the adsorption affinity ofaminomethylenephosphonate for HAP, the adsorption affinityof the 188 Re-amp complex for HAP increased in the order
188
Re-EDBMP<188Re-NTMP<188Re-EDTMP. The order of theadsorption affinity of the 188Re-amp complex obtained in thisstudy corresponds to the number of phosphonate groups inaminomethylenephosphonate, supporting that the interaction
between phosphonate groups in the 188Re-amp complex andcalcium ions on the surface of HAP was one of major factors
in terms of the adsorption affinity of 188Re-amp for HAP.
As shown in Figures 5 and 6, the adsorption coefficient ofcarrier-free 188Re-EDTMP was larger than that of carrier-addedone (20 µg/ml) under the same conditions. From the linear
isotherm as shown in Figure 4, the adsorption coefficient of the188
Re complex should be independent of the Re carrier concentration. In order to clarify the effect of carrier, the influence ofthe concentration of the Re carrier on the adsorption coefficient of 188Re-EDTMP was examined in detail. The adsorption
coefficient was constant in the range from carrier-free to 0.002µg/ml, but decreased with increasing the concentration of theRe carrier in the 188Re-EDTMP sample over 0.002 µg/ml to 20µg/ml, as shown in Figure 8. Rhenium-diphosphonate
complexes, as well as technetium complexes, are thought to bea mixture of polymeric complexes containing tin (Sn) by
HPLC analysis5, 8 and EXAFS data.42 And the ratio of thesecomponents of technetium-diphosphonates is known to depend

0.0002 µg

carrier-free
0

10
20
30
Retention time / min40

Figure 9. Effect of the carrier concentration on the ion-paired
reversed phase HPLC chromatogram of 188Re-EDTMP.

Adsorption of 188Re Complexes with Aminomethylenephosphonate

on the formation conditions such as pH, adding the carrier, theconcentration of diphosphonate and the difference of reductant(SnCl2 or NaBH4).43−46 And, the analysis of 188Re-EDTMP by
ion-paired reversed phase chromatography showed that thechromatogram of carrier-free complex was different from thatof carrier-added complex.47 The effect of the concentration of
Re on the chromatogram of 188Re-EDTMP was examined byion-paired reversed phase chromatography, as shown in Figure
9. The chromatogram was almost constant in the range fromcarrier-free to 0.002 µg/ml, but changed gradually withincreasing the concentration of the Re carrier over 0.002 µg/ml
to 20 µg/ml. The change of the chromatogram corresponded
to the change of adsorption coefficient. In conclusion, theeffect of the concentration of Re on the adsorption coefficient
was caused by the different distribution of the components in
the 188Re-EDTMP mixture between the carrier-free and thecarrier-added complex.
Acknowledgement. The authors are grateful to Dr.
Tsutomu Sekine of Tohoku University for his fruitful discussions in this study.
References(1) V. J. Lewington, Eur. J. Nucl. Med. 20, 66 (1993).
(2) L. F. Mausner and S. C. Srivastava, Med. Phys. 20, 503(1993).
(3) H. Vera-Ruiz, IAEA Bulletin 35, 24 (1993).
(4) A. P. Callahan, D. E. Rice, and F. F. Knapp, Jr.,
NucCompact 20, 3 (1989).
(5) M. Eisenhut, Int. J. Appl. Radiat. Isot. 33, 99 (1982).
(6) K. Hashimoto, S. Bagiawati, M. Izumo, and K.
Kobayashi, Appl. Radiat. Isot. 47, 195 (1996).
(7) L. Mathieu, P. Chevalier, G. Galy, and M. Berger, Int. J.
Appl. Radiat. Isot. 30, 725 (1979).
(8) E. Deutsch, K. Libson, J-L. Vanderheyden, A. R. Ketring,and H. R. Maxon, Nucl. Med. Biol. 13, 465 (1986).
(9) H. R. Maxon, E. A. Deutsch, S. R. Thomas, K. Libson, S.
J. Lukes, C. C. Williams, and S. Ali, Radiology 166, 501(1988).
(10) J. M. H. de Klerk, A. D. van het Schip, B. A. Zonnenberg,
A. van Dijk, M. P. M. Stokkel, S. H. Han, G. H. Blijham,and P. P. van Rijk, J. Nucl. Med. 35, 1423 (1994).
(11) Y. Arano, M, Ono, K. Wakisaka, T. Uezono, H. Akisawa,
Y. Motonari, Y. Makata, J. Konishi, and A. Yokoyama,
Radioisotopes 44, 514 (1995).
(12) H. S. Bai, X. H. Jin, F. Wang, J. Du, Y. M. Liu, and D. M.
Chen, J. Radioanal. Nucl. Chem. Art. 206, 43 (1996).
(13) K. Hashimoto, Appl. Radiat. Isot. 49, 351 (1998).
(14) L. Qingnuan, Z. Xiaodong, S. Rong, and L. Wenxin, Appl.
Radiat. Isot. 53, 993 (2000).
(15) S. Alyafei, K. Tomiyoshi, M. Sarwar, K. Ahmed, H.
Zhang, N. Oriuchi, T. Inoue, and K. Endo, Nucl. Med.
Comm. 20, 551 (1999).
(16) C. Arteaga de Murphy, G. Ferro-Flores, M. PedrazaLópez, L. Meléndez-Alafort, B. Y. Croft, Flor de María
Ramírez, and J. Padilla, Appl. Radiat. Isot. 54, 435 (2001).
(17) H. R. Maxon III, L. E. Schroder, S. R. Thomas, V. S.
Hertzberg, E. A. Deutsch, H. I. Scher, R. C. Samaratunga,
K. F. Libson, C. C. Williams, J. S. Moulton, and H. J.
Schneider, Radiology 176, 155 (1990).
(18) J. M. S. P. Quirijnen, S. H. Han, B. A. Zonnenberg, J. M.
H. de Klerk, A. D. van het Schip, A. van Dijk, H. F. J. ten
Kroode, G. H. Blijham, and P. P. van Rijk, J. Nucl. Med.
37, 1511 (1996).
(19) S. H. Han, B. A. Zonnenberg, J. M. H. de Klerk, J. M. S.
P. Quirijnen, A. D. van het Schip, A. van Dijk, G. H.

J. Nucl. Radiochem. Sci., Vol. 2, No. 1-2, 2001

9

Blijham, and P. P. van Rijk, J. Nucl. Med. 40, 639 (1999).
(20) R. Sciuto, A. Tofani, A. Festa, D. Giannarelli, R.
Pasqualoni, and C. L. Maini, J. Nucl. Med. 41, 647(2000).
(21) H. Kolensnikov-Gauthier, P. Carpentier, P. Depreux, P.
Vennin, A. Caty, and C. Sulman, J. Nucl. Med. 41, 1689
(2000).
(22) W. F. Goeckeler, B. Edwards, W. A. Volkert, R. A.
Holmes, J. Simon, and D. Wilson, J. Nucl. Med. 28, 495(1987).
(23) A. Singh, R. A. Holmes, M. Farhangi, W. A. Volkert, A.
Williams, L. M. Stringham, and A. R. Ketring, J. Nucl.
Med. 30, 1814 (1989).
(24) J. C. Lattimer, L. A. Corwin, Jr., J. Stapleton, W. A.
Volkert, G. J. Ehrhardt, A. R. Ketring, S. K. Anderson, J.
Simon, and W. F. Goeckeler, J. Nucl. Med. 31, 1316
(1990).
(25) C. Collins, J. F. Eary, G. Donaldson, C. Vernon, N. E.
Bush, S. Petersdorf, R. B. Livingston, E. E. Gordon, C. R.
Chapman, and F. R. Appelbaum, J. Nucl. Med. 34, 1839
(1993).
(26) A. S. Alberts, S. W. Brighton, P. Kempff, W. K. Louw, A.
V. Beek, V. Kritzinger, H. P. Westerink, and A. J. van
Rensburg, J. Nucl. Med. 36, 1417 (1995).
(27) A. J. Tofe and M. D. Francis, J. Nucl. Med. 15, 69 (1974).
(28) A. van Langevelde, O. M. J. Driessen, E. K. J. Pauwels,
and C. W. Thesingh, Eur. J. Nucl. Med. 2, 47 (1977).
(29) M. D. Francis, D. L. Ferguson, A. J. Tofe, J. A. Bevan,and S. E. Michaels, J. Nucl. Med. 21, 1185 (1980).
(30) M. W. Billinghurst, D. Jette, and E. Somers, Int. J. Appl.
Radiat. Isot. 32, 559 (1981).
(31) J. Kroesbergen, A. M. P. van Steijn, W. J. Gelsema, andC. L. de Ligny, Int. J. Nucl. Med. Biol. 12, 411 (1986).
(32) R. A. M. J. Claessens and Z. I. Kolar, Langmuir 16, 1360
(2000).
(33) D. Chirby, S. Franck, and D. E. Troutner, Appl. Radiat.
Isot. 39, 495 (1988).
(34) L. Shunzhong, Q. Jian, P. Manfei, L. Zhonglin, Z. Pengji,
and F. Yibei, Nucl. Sci. Tech. 6, 241 (1995).
(35) K. Hashimoto, Appl. Radiat. Isot. 51, 307 (1999).
(36) K. N. Kushita and J. Du, Appl. Radiat. Isot. 49, 1069
(1998).
(37) P. Somasundaran and Y. H. C. Wang, in Adsorption on
and Surface Chemistry of Hydroxyapatite, edited by D. N.
Misra (New York, USA: Plenum Press, 1984), p. 129.
(38) H. Tanaka, Y. Nuno, S. Irie, and S. Shimomura, Talanta
39, 893 (1992).
(39) P. Ducheyne, C. S. Kim, and S. R. Pollack, J. Biomed.
Mater. Res. 26, 147 (1992).
(40) T. V. Vasudevan, P. Somasundaran, C. L. Howie-Meyers,
D. L. Elliott, and K. P. Ananthapadmanabhan, Langmuir
10, 320 (1994).
(41) D. T. H. Wassell, R. C. Hall, and G. Embery, Biomaterials
16, 697 (1995).
(42) R. C. Elder, J. Yuan, B. Helmer, D. Pipes, K. Deutsch, and
E. Deutsch, Inorg. Chem. 36, 3055 (1997).
(43) S. Tanabe, J. P. Zodda, E. Deutsch, and W. R. Heineman,Int. J. Appl. Radiat. Isot. 34, 1577 (1983).
(44) M. V. Mikelson and T. C. Pinkerton, Anal. Chem. 58,
1007 (1986).
(45) J. P. Zodda, S. Tanabe, W. R. Heineman, and E. Deutsch,
Appl. Radiat. Isot. 37, 345 (1986).
(46) G. J. de Groot, H. A. Das, and C. L. de Ligny, Appl.
Radiat. Isot. 38, 611 (1987).
(47) K. Hashimoto, Abstract of Papers, The Second JapaneseRussian Seminar on Technetium, Shizuoka, Japan, Nov.
29-Dec. 2, 1999; paper 3006.