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Iodine-123 production for radiopharmaceuticals—XX
International Journal of Applied Radiation and Isotopes, 1977, Vol. 28, pp. 395-40i. Pergamon Press. Printed in Northern Ireland
Iodine-123 Production for Radiopharmaceuticals--XX* Excitation Functions of the '24Te(p, 2 n)i23I and i24Te(p, n)I24I Reactions and the Effect of Target Enrichment on Radionuclidic Purityt K. K O N D O , R. M. L A M B R E C H T and A. P. W O L F Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973, U.S.A.
(Received 28 June 1976) The excitation functions for the 124Te(p, 2n)123I and 124Te(p, n)iZ4I reactions were determined with thin films of 99.87% and 91.86% isotopically enriched 124Te. The production rates and the optimum fractions of the excitation functions for obtaining the maximum radiochemical purity of 123I with the different isotopic enrichments of a24Te were established. Targetry, radiochemistry and a quantitative procedure for recovery of ~24Te are to be described in a subsequent paper. The 124Te(p, 2n)a23I reaction on ultrahigh enrichment ~24Te is a satisfactory and economical production method on cyclotrons with particle energies or beam intensities too low to produce 123Xe as a source of high-purity iodine123. The 122Te(d, n)123I, a24Te(p,2n)123L 123Te(p, INTRODUCTION IODINE-123 was recognized ~2) in 1962 as an n)123I and 121Sb(c~,2n)123I reactions have ideal nuclide for most radiopharmaceutical been in routine use. (3' 19-24) However, the applications involving radioiodine for diagnos- 123I produced by direct nuclear reactions altic procedures requiring 24 hr or less. ways results in i231 containing variable levels Nevertheless, it cannot be overemphasized of radionuclidic impurities of a24I, 125I, 13°1, that the advantages ~3) of high purity 1 2 3 I a r e a etc. Earlier researchers ¢16-18'23) have sug123 I lower radiation exposure to the patient ~4) and gested that the radionuclidic quality of from the direct nuclear reactions might be at the high quality scintiphotos ~5) that can be least partially alleviated if 124Te, a23Te or obtained. The excellent review of MYERS(3) summarizes the progress and status of 1231 122Te were available in an ultra-high isotopic through 1973. The highest purity 1231 now enrichment. However, it is probably not practical to obtain 123Te in an enrichment necesavailable is produced with the 123Xe ~ 2 'hr 1 123i sarylto allow high purity 123I production via ~+,EC the 23Te(p, n)lZ~I reaction. generator. ~I-~9) The limitation of the generator The characteristics of the cyclotrons presis that the required particle energies are not ently being utilized for radionuclide producattainable with compact medical cyclotrons. tion for radiopharmaceuticals vary considerably a m o n g institutions. There is a pressing need for detailed information on production * For earlier papers in this series, see ref. 1. All yields and radionuclidic purities under a varienquiries should be directed to R. M. Lambrecht. ety of operating conditions, in order that a t Research performed at Brookhaven National given facility can decide which production Laboratory under contract with the U.S. Energy Research and Development Administration, and method and irradiation conditions to use. The 12aTe(p, 2n)123I reaction was suggested ~z) partially supported by NIH Grant No 5. P41 in 1962. The early reports (16'2s'26) of RR00657. 395
396
K. Kondo, R. M. Lambrecht and A. P. Wolf
the high production yield encouraged examination of the production method. Based on our results ~16) at 28 MeV, a request
COLLIMATOR ( 5/B inch)
r+ V A V / / / / / / / ~ A A
.PERMANENT MAGNETS . r ~ ( ~ tOOOG see inserf below) .......
~ V///Z/'7///A I OTON BEAM
~
.... I
E223 E223 1.4//A.~/////////A NYLON ~ 1 I N SULATORS ~ TO EARTH
I
/ AI WINDOW
AXIS
1 T TO CURRENT INTEGRATOR
PROTON
PROTON BEAM
___
AI ~ " ~
~
POLYSTYRENE -/ Te FILM
Cu
FIG. 1. Experimental arrangement for measurements of excitation functions on the BNL 60 in. cyclotron.
EXPERIMENTAL M e a s u r e m e n t o f excitation functions
Isotopic enrichments of a24Te to 91.86% and 99.87% were purchased from Isotope Sales at O a k Ridge National L a b o r a t o r y at a cost of $1.75/mg and $15.00/mg, respectively. The percentage composition of Te isotopes in each e m i c h m e n t are listed in Table 1. The excitation functions were determined by the method of stacked, thin targets. Each target consisted of 1.05 + 0 . 0 1 mg T e / c m 2 uniformly suspended in a self-supporting polystyrene film. (31) TABLE 1. Isotopic composition of enriched 124Te % Isotopic enrichment* 91.86% 99.87%
12°Te
< 0.02
lZ2Te
0.49 0.11 91.86 3.17 1.81 1.55 1.05
123Te 124Te 125Te
126Te 128Te 13°Te
< 0.002 < 0.003 0.006 99.87 0.095 0.020 <0.010 < 0.008
* As reported by ORNL.
The powdered 124Te ( - 1 . 2 g) was uniformly suspended in 1.67 g of polystyrene and 23.9 ml of benzene. The solution was quickly
poured onto a clean, flat, Pyrex plate and allowed to dry at r o o m t e m p e r a t u r e for 1 hr. The advantages of the method is that a n u m b e r of uniformly thin Te targets can be conveniently prepared. The enriched 124Te is easily recovered as the support only contains C and H. The disadvantage is the poor thermal conductivity of the target which necessitates using a low intensity, diffused b e a m for the b o m b a r d m e n t s . The Te concentration in each target was determined at the conclusion of the experiment by dissolution in conc HNO3 and 72% HC104, and X-ray fluorescence spectrometry. The thin targets were stacked between A1 and Cu foils as b e a m degraders. The energy loss was calculated. (32) All irradiations were p e r f o r m e d on the B N L 60 in. cyclotron. The uncertainty in the incident proton b e a m energy was estimated as 1%. A highly defocussed, diffused and collimated proton b e a m was used for all measurements. The integrated b e a m was measured with a Faraday Cup in which a crossed 1 k G magnetic field was used to suppress secondary electrons. (See Fig. 1.) Cu foil monitors (12.57 mg/cm 2) employing the 63Cu(p, n)63Zn cross sections reported by COLLE e t a / . (33) gave an integrated flux which agreed within 1% of the value obtained with the Faraday Cup. The typical irradiation condition was 0.5 txA for 200 sec. The reaction cross sections were calculated by the usual method.
397
Iodine-123 production for radiopharmaceuticals-XX Non-destructive
measurements
2. Cross sections for the 124Te(p,2n)? and 124Te(p, E)‘*~I reactions on 99.87% isotopic
TABLE
After the bombardment each target was enrichment “‘Te mounted in a calibrated geometry in front of a 123 124 high-resolution Ge(Li) detector calibrated for I I efficiency with National Bureau of Standards u (mbarn) u (mbarn) sources. The distinct y-lines and half-lives were sufficiently distinguishable without 436.2rt34.9 43.7izl1.4 28.19kO.30 34.9k6.8 649.8 ~~68.8 chemical separation. To minimize systematic 26.43 f 0.34 37.3 zt 15.6 1017.9* 107 25.3610934 errors a Northern Scientific 4096 channel 30.5 f 8.2 914.4k45.7 24.10zt0.37 analyzer with 2-point digital stabilization was 53.815.8 1011.4zk59.6 22.65 *to.40 used. The dead-time losses were always less 889.6~69.5 65.6*4.0 20.86*0.41 than 10%. 84.8+ 13.9 630.9 It 70.5 18.82kO.45 The principal photopeaks of each nuclide 194.9 f 16.2 427.7kSl.l 16.35 *0.70 were followed to establish the half life and 455.5 k29.6 160.6* 6.4 14.54~t 0.72 confirm the identity of the nuclide. The 308.9* 38.8 24.515.6 12.45 f 0.79 Brookhaven decay curve analysis program, 115.9* 18.8 9.95kl.10 CLSQ, and a modified version of the spectral analysis program, BRUTAL, were used for the data reduction. (34)The Nuclear Data(33’ 35) TABLE 3. Cross sections for the lz4Te(p, 2n)lz31 y-lines, and the (abundance) used are: lz31 and lz4Te(p, n)12’? reaction on 91.86% isotopic enrichment lz4Te (13.3 hr, 159 keV, 83%), lz41 (4.17 days, 603 keV, 67%), and “3Zn (38.0 min; 670 keV, ‘23 124 I I 8.47% and 962 keV, 6.68%). P (mbarn) u (mbarn) The counting error at the 95.5% confidence level for lz31 and “‘1 was less than 3%. The 99.5k 19.9 32.4zt7.8 29.181tO.29 greatest errors arise from the uncertainties in 392.3k51.0 29.12*0.29 43.6rt9.6 the irradiation parameters resulting from any 615.Ozk37.8 27.4OzkO.30 66.1 f 10.9 lack of uniformity in the tellurium thickness 1066.4+111..5 25.64 f 0.34 86.8 * 10.5 (<2%), and specifically from heterogeneous 843.5 f 70.2 25.62zt0.34 59.6zk8.3 1137.8k68.2 distribution, if any. Impuritjes present in the 24.5OzkO.37 74.4*5.9 1037.7zt 103.8 24.44 i 0.37 70.5 * 8.7 target other than Te were < 1%. Recoil losses 838.8+98.9 22.58izO.40 68.5 f 8.9 of 231 and lz41 from the polystyrene matrix 867.8zt91.1 22.38~0.40 63.9* 6.7 were very small and were neglected in com904.1 ~k45.2 21.34*0.30 87.7k7.2 puting the cross sections. Overall errors are 912.6zt 77.6 20.18?~0.41 117.0*14.0 typically of the order of 12%, although rela740.2 zk50.3 19.04*0.43 167.3 zt23.6 tive errors for comparative yields from the 615.4k67.7 17.74+0.55 180.7 + 17.0 various reactions would be considerably smal512.7~~65.4 17.42zk0.59 376.8 rt 26.4 ler, since systematic uncertainties in detector 515.3k41.2 16.22 ztO.70 445.6+ 33.4 efficiencies and nuclear decay properties 52.9zk 12.7 14.34zt0.72 440.6 f 24.2 would be removed. 53.7* 18.7 13.33 zto.75 419.1*33.9 12.20*0.80
RESULTS Excitation
AND
DISCUSSION
functions
The 124Te(p, 2n)‘231 and rz4Tefp, n)lz41 reaction cross sections were determined for incident proton energies of 28.19-9.95 MeV for lz4Te of 99.87% isotopic enrichment; and from 29.18 to 12.20 MeV on ‘24Te of 91.86% enrichment. The experimental results are presented in Tables 2 and 3 and Figs. 2 and 3,
5.8+x6.0
237.6 f 28.5
respectively. In general, the excitation functions exhibit the expected trends for (p, a) and (p, 2n) reactions on nuclides of intermediate mass. However, certain details require elaboration. The ‘24Te(p, 2n)‘231 reaction has a flat maximum cross section of about 1 barn in the range of 23.5-25.5 MeV. The (p, n) reaction has a maximum cross section of about
398
oZ
K. Kondo, R. M. Lambrecht and A. P. Wolf A salient point is that the total cross section for formation of 1241 is substantially reduced (by about a factor of - 2 in the optimum section of the excitation functions) if ultrahigh enrichment 124Te is used.
tO0
H
/ I0
9'86%
/
I 8
I I0
'24Te
"I
o 12~ ~
I 12
I _1 I t [ I 14 16 18 20 22 24 PROTON ENERGY, MeV
Production yields and radionuclidic purity
j
I 26
i
I 28
IJ 50
_FIG. 2. Excitation functions for 123I and 1241by proton irradiation of 124Te of 91.86% isotopic enrichment. 450 mbarn at about 14.5 MeV. It is important to note the differences in the shapes of the excitation functions (cf. Figs. 2 and 3) with 124Te of 99.87% and 91.86% enrichment. The appearance of structure in the excitation functions at incident proton energies greater than 18 MeV is more evident with 91.86% enrichment XEgTe. The total cross section leading to 123I via the 123Te(p, n)123I reaction is estimated as -<1% for either enrichment of 124Te. However, the 91.86% 124Te contains 3.17% 125Te (Table 1). The 125Te(p, 3n)~23I 125Te(p, 2n)X24I reactions are likely making an appreciable contribution to the yield of 123I at Ep > 2 5 MeV, and the yield of 1241 at Ep > 16.5 MeV. [-
I
[
F
T
99.87%
Ioo0~
i-"-
]
I - - T ~ - - T
I
I -]
i24Te
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~
o
_ 4
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q
12
I
14
[
I
I
16 ll8 20 22 214 PROTON ENERGY, MeV
I
26
k
28
~
50
Fio. 3. Excitation functions for 123I and 1241by proton irradiation of t24Te of 99.87% isotopic enrichment.
Absolute cross-section measurements for the 124Te(p, 2n)123I reaction have not been previously reported. However scattered data have appeared concerning various aspects of the production rates and the resulting radionuclidic purity (see Table 4 and Fig. 4). Figure 4 depicts the production rates as a function of the proton energy on our targets of 91.86% enrichment 124Te. The yields, expressed as mCi/tzAhr, were calculated using the cross section data reported in Table 3, and assuming a target thickness of 1.0 MeV irradiated at a fluence of 1.0/xA for 1.0 hr. For comparison the production rates reported by ACERBI e t al. (2°) are also presented. It is apparent that the yield data of the two groups are in general agreement (but the BNL data are lower) if the energy axis is translocated to the right for the University of Milan data. T h e ~ r o d u c t i o n yields integrated over various 12 Te target thickness are compared in Table 4. Several discrepancies occur. The differences are probably attributable to the isotopic enrichment of the 124Te targets, the target thickness, uncertainties in the cyclotron proton energies, and in one case (26) a large uncertainty in detector efficiency calibrations. It is unfortunate that many papers published on isotope production for radiopharmaceutical applications do not report the nuclear data which was used. However, the production data in Table 4 can be summarized if we neglect the effects of isotropic enrichment. At 25 MeV with 415-420 mg/cm 2 targets, production yields of 14.7, 24.3, and 17.5 mCi//xAhr are reported by DEGLUME eta/., (25) ACERBI et al. (2°) and this work, respectively. For 256 mg/cm 2 targets at incident proton energies of - 2 7 and 25.8 MeV, the production rates reported by BEAVER(28' 29) and this work are comparable at -->10 mCi/txAhr. There is a serious disagreement in the expected and obtained yields of CAUWE et a/. (26),
399
Iodine-123 production for radiopharmaceuticals-XX
TABLE4. A comparison of production yield and radionuclidic purity data reported for the ‘24Te(p, 2n)IZ31 reaction under a variety of production
Reference (16) (2.5) (28,29) iz”:; This work
Production rate mCi/FAhr
conditions
Ep (MeV) incident
Target thickness m&m2
‘24Te (%) enrichment
27.8 25 30 27’“’
19.6 420 910 22.5
96.2 95 95 96.21
0.54 14.7 25.0 Z 10.(Yd’
0.5’“’ ib) (b1 0 78’“’
25 30 28 25.8 27 26 2.5 28
415 900 930 256 519 346 415 912
91.86 93.4 91.86 99.87 99.87 91.86 91.86 91.86
25(40)“’ 24.3 45 10.6 20.4 14.9 17.5 33.6
(bj 0.72 0.88 0.54 0.62 1.0 1.11 -
Radionytlidic 124I I 0 01
-1 0.0011 -
ptn$y at EOB 130 I I o.o? 1 0.0014 -
1 0.03 1 -
w Typographical error occurred in Table 2 of ref. 16 and reported the level as 0.05%. (U lz41 reported as l&2.4% radiotoxicity relative to pure I3 I. “) Actual proton energy entering the lz4Te c 27 MeV. w Routinely produce 2200 mCi/hr with a 20 &A ffuence. w Based on assay of 50 routine production lots. (f)The authors state “The accuracy of the yield figures is about 25% resulting mainly from the inaccurate knowledge of the target thickness, the error on the current measurement and on the efficiency calibration of the GeLi detector.”
I/
I)
PROTON
‘*‘I
ACERBl
n ‘?
THIS
‘
ACERBI
lz41
ENERGY
etol. WORK
i
MeV thickness irradiated with 28 MeV protons, the production rate reported by ACERBI et ~1.~~‘)was 45 mCi/pAhr; whereas we report 33.6 mCi/pAhr. However, DEGLUMEet uL(~~) reported a production rate of 25.0 mCi/pAhr for 30 MeV proton irradiation of 910 mgicm’ targets.
et al.
(MeV!
FIG. 4. A comparison of the production rates of 123I and I“‘1 on ‘24Te of 91.86% isotopic enrichment as reported by ACERBIet al. (ref. 20) and obtained in this work.
cf. 2.5 mCi/~Ahr and 40 mCi/pAhr, respectively, for 30 MeV proton on 900 mg/cm’ of f24Te enriched to 93.4%. With targets of - 11
The highest quality 1231, that is obtainable by a route alternate to the ‘23Xe-+1231 generator, is via the ‘24Te(p, 2n)1231 reaction lz4Te of ultrahigh isotopic enrichment The Gization of 99.9% vs. 91.8% 124Te incrkases the radionuclidic purity relative to 124I by a factor of nearly 2. Various data reported by other laboratories (see Table 4) clearly support this conclusion. We routinely use 99.87% 12*Te and an incident proton energy of 25.8 MeV on targets consisting of 80-256 mg/cm ’ ‘24Te with 3 hr irradiations at a ffuence of 10-15 @A (our maximum current available) to produce lz31 with <0.65% 1241at
I(. Kmdo,
400 R fmg 894
18
20
1048 /
22
PROTOW
R. M. ~u~~rec~t and A. P. Wolf
Te/cm*) 1212 /
1385 I
24
26
1567 I
28
ENERGY,MeV
FIG. 5.
Influence of incident proton energy, target compositio’n, target thickness and time on the radionuclidic quality of lz31. the time of use. The other radionu~lidic $purities present are lZ51 (1.1 X 10s3%), I (1.4x 1K3%) and 13’1 (3.1 x lo-“%). Within the limits of detection (~10-~%) 13’1 was absent. Figure 5 summarizes the optimum conditions we have determined for the production of lz31 via the 124Te(p, 2n)lz31 reaction with lz4Te of 99.87% and 91.86% enrichment. The results are given fqr short irradiation conditions. The per cent lz41 relative to ‘*? at the end of bombardment is given on the left side of Fig. 5 for various incident proton energies. The range of protons in Te is given on the top of the figure. The right side of Fig. 5 depicts a time scale which can be used to read the level of lz41 which arises as a function of time following the irradiation. It is clearly evident that by using ultra-high enrichment 24Te the radionuclidic purity at the end of production is enhanced by a factor of 2. The upper 1eve11F3n I the per cent lz41 that is acceptable in a radiopharmaceutical depends somewhat on the diagnostic use. For example, in terms of radiation dose delivered to the patient, a few per cent lZRI in ‘231-ortho-iodohippuran (a
renal agent) delivers a lower radiation dose, than does the same amount of lz41 in 1231iodide for thyroid scans. A second factor is the effect of the higher energy photons of 1241 (511, 604 keV) on the degradation of the scintiphotos. For many radiopharmaceutical applications, not requiring ultra-pure Y, it has been considered that about 5% Iz41 is acceptable!“@ 37f Therefore utilization of a 256 mglcm’ target of 99.87% IZ4Te at an incident proton energy of 25.8 MeV will result in lz31 with a shelf-life of >40 hr. The lz4Te(p, 2n)? reaction, while second best in radionuclidic purity to the 1*3Xe-‘2”T generator, does result in a high production yield which is comparable in fact to the yield of the lZ71(p,58)“’ Xe+ lZ31 generator. Utilization of the optimum production conditions on a target of ultra-high isotopic enrichment lz4Te is a promising and acceptable route to providing 231 for radiopharmaceutical applications. REFERENCES 1. LAMBRECHT R. M. and WOLE‘ A. P. Radiat. Res. 52, 32 (1972). 2. MYERS W. G. and ANGER H. 0. J. rztrcl. Med. 3, 183 (1962). 3. MYERS W. G. In Recent Ad~unces in Nuclear Medicine (Edited by LAWRENCE J. H.), pp. 131-160. Grune & Stratton, New York (1974). 4. WELLMAN I-I. N. and ANGER R. T., JR. Seminars in Nucl. Med. 1, 356 (1971). J. F., LAhloREcHr R. 5. ATKINS H. L., KLLWPER M. and WOLF A. P. Am. J. R(~~~~tge~~i., Radial. Therapy nucl. Med. 117, 195 (3973). 6. SODD V. J., BLUE J. W. and WELLMAN H. N. CIyclotron production of ‘23I. An evaluation of the nuclear reactions which produce this isotope. ~~~~M~E 70-4. 38 pp. U.S. Dept. of Health, Education and Welfare (October 1970). 7. BLUE J. W. and SODD V. J. In Uses of Cyclotrons in Chemistry, Metallurgy und Biolagy (Edited by AMPHLETT C. B.) pp. 138-147. 3utterworths, London (1970). C., REDVANLY s. LAMBRECHTR. M., MANTESCU C. S. and WOLF A. P. I. nud. Med. 13, 266 (1967). 9. LINDNERL., BRINK~~ANG. A., SUER T. H. G., SCHXMMELA., VIXNBOI~.RJ. TH., KARTEN F. H. S., V~SSER J. and LEURS C. J. in Rudi~p~ar~aceuticals and labeled Co~~~u~ds Vol. 1. pp. 308-316. Vienna, IAEA (1973).
Iodine-123 production for radiopharmaceuticals--XX 10. STANG L. G., JR., HILLMAN M. and LEBOWITZ E. The Production of Radioisotopes by Spallation. B N L Report 50195, T-547 (1969). 11. F v s c o M. A., PEEK N. F., JUNGERMAN J. A., ZIELINSKI F. W., DENARDO S. J. and DENARDO G. L. J. nucl. Med. 13, 729 (1972). 12. WEINREICH R., SCHULT O. and STOCKLIN G. Int. J. appl. Radiat. Isotopes 25, 535 (1974). 13. LEBOWtTZ E., GREENE M. W. and RICHARDS P. Int. J. appl. Radiat. Isotopes 22, 489 (1971). 14. LOBER~ M. D., PHELPS M. E. and WELCH M. J. J. nucl. Med. 14, 733 (1973). 15. GUILLAUME M., LAMBRECHT R. M. and WOLF A. P. Int. J. appl. Radiat. Isotopes 26, 703 (1975). 16. LAMBRECHT R. M. and WOLF A. P. In Radiopharmaceuticals and Labeled Compounds Vol. 1, pp. 275-290. Vienna, I A E A (1973). 17. LAMBRECHT R. M. and WOLF A. P. Int. Symp. of Radiopharmaceuticals, Atlanta, Georgia, 11-15 February, 1974. In Radiopharmaceuticals (Edited by SUBRAMANIAN G., RHODES B. A., COOPER J. F. and SODD V. J.) pp. 111124. Society of Nuclear Medicine, New York (1974). 18. ACERBI E., BIRATrARI C., CASTIGLIONI M., RESMINI F., SPAVIERI I. and VILLA G., Production of 123I for medical purposes at the Milan A V F cyclotron. Paper presented at the 11th European Cyclotron Progress meeting, 29 May-1 June (1974). 19. SODD V. J. In Radiopharmaceuticals (Edited by SUBRAMANIANG., RHODES B. A., COOPER J. F. and SODD V. J.) pp. 125-133. Society of Nuclear Medicine, New York (1975). 20. ACERBI E., BIRATTARI C., CASTIGLIONI M. and RESMXNI F. Int. J. appl. Radiat. Isotopes 26, 741 (1975). 21. ACERBI E., BIRATTARI C., CASTIGLIONI M., RESMINI F. and SPAWERI G. Nederlands Tijdschrift Voor Natuurkunde 22, 332 (1973). 22. RHODES G. A., WAONER H. N., JR. and GERRARD M. Isot. Radiat. Technol. 4, 275 (1967). 23. HUPF H. B., ELDRIDGE J. S. and BEAVER J. E. Int. J. appl. Radiat. Isotopes 19, 345 (1968). 24. SILVESTER D. J., SUYDEN J. and WATSON I. A.
401
Radiochem. Radioanal. Lett. 2, 17 (!969). 25. DEGLUME C., DEUTSCH J. P., FAVART D. and PRIEELS R. Int. J. appl. Radiat. Isotopes 24, 291 (1973). 26. CAUWE F., FEUTSCH J. P., FAVART D., PRIEELS R. and COGNEAU M. Int. J. appl. Radiat. Isotopes 25, 187 (1974). 27. LAMBRECHT R. M and DAvis W. C. Private communication (1973). 28. BEAVER J. E. In Proc. Conf. Thyroid and Endocrine System Investigations with Radionuclides, Miami Beach, Florida, (March, 1974) (to be published). 29. BEAVER J. In Proceedings of a meeting on Iodine-123 Applications in Nuclear Medicine, H E W Publication (FDA) 76-8033, pp. 48-49, 98-102. Bureau of Radiological Health (May 1975). 30. LAMBRECHT R. M., KONDO K. and WOLF A. P. In Proceedings of a meeting on Iodine-123 Applications in Nuclear Medicine. H E W Publications (FDA) 76-8033, pp. 86-91. Bureau of Radiological Health (May 1975). 31. WALL N. S. and IRVINE J. W. Rev. Sci. Instr. 24, 1146 (1953). 32. WILLIAMSON C. F., BouJoT J. P. and PICARD J. Rapport CEA-R-3042 (1966). 33. COLLE R., KISHORE K. and CUMMING J. B. Phys. Rev. C 9, 1819 (1974). 34. (a)CUMMING J. B. National Academy of Sciences-National Research Council. Nuclear Science Series Report No. NAS-NS-3107, 1962 (unpublished). (b) GUNNINK R., LEVY H. B. and NIDAY J. B. University of California Radiation Laboratory Report No. UCID-15140 (unpublished); modified by B. Erdal (unpublished). 35. AUBLE R. L. Nuclear Data Sheets B7, 363, 465 (1972). 36. PARAS P. Overview of Alternatives to 131I Use for Thyroid Diagnosis. Report, Bureau of Radiological Health, Rockville, Md. 20852 available on request. 37. DAHL J. R. and TILBURY R. S. Int. J. appl. Radial. Isotopes 23, 431 (1972).
Iodine-123 Production for Radiopharmaceuticals--XX* Excitation Functions of the '24Te(p, 2 n)i23I and i24Te(p, n)I24I Reactions and the Effect of Target Enrichment on Radionuclidic Purityt K. K O N D O , R. M. L A M B R E C H T and A. P. W O L F Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973, U.S.A.
(Received 28 June 1976) The excitation functions for the 124Te(p, 2n)123I and 124Te(p, n)iZ4I reactions were determined with thin films of 99.87% and 91.86% isotopically enriched 124Te. The production rates and the optimum fractions of the excitation functions for obtaining the maximum radiochemical purity of 123I with the different isotopic enrichments of a24Te were established. Targetry, radiochemistry and a quantitative procedure for recovery of ~24Te are to be described in a subsequent paper. The 124Te(p, 2n)a23I reaction on ultrahigh enrichment ~24Te is a satisfactory and economical production method on cyclotrons with particle energies or beam intensities too low to produce 123Xe as a source of high-purity iodine123. The 122Te(d, n)123I, a24Te(p,2n)123L 123Te(p, INTRODUCTION IODINE-123 was recognized ~2) in 1962 as an n)123I and 121Sb(c~,2n)123I reactions have ideal nuclide for most radiopharmaceutical been in routine use. (3' 19-24) However, the applications involving radioiodine for diagnos- 123I produced by direct nuclear reactions altic procedures requiring 24 hr or less. ways results in i231 containing variable levels Nevertheless, it cannot be overemphasized of radionuclidic impurities of a24I, 125I, 13°1, that the advantages ~3) of high purity 1 2 3 I a r e a etc. Earlier researchers ¢16-18'23) have sug123 I lower radiation exposure to the patient ~4) and gested that the radionuclidic quality of from the direct nuclear reactions might be at the high quality scintiphotos ~5) that can be least partially alleviated if 124Te, a23Te or obtained. The excellent review of MYERS(3) summarizes the progress and status of 1231 122Te were available in an ultra-high isotopic through 1973. The highest purity 1231 now enrichment. However, it is probably not practical to obtain 123Te in an enrichment necesavailable is produced with the 123Xe ~ 2 'hr 1 123i sarylto allow high purity 123I production via ~+,EC the 23Te(p, n)lZ~I reaction. generator. ~I-~9) The limitation of the generator The characteristics of the cyclotrons presis that the required particle energies are not ently being utilized for radionuclide producattainable with compact medical cyclotrons. tion for radiopharmaceuticals vary considerably a m o n g institutions. There is a pressing need for detailed information on production * For earlier papers in this series, see ref. 1. All yields and radionuclidic purities under a varienquiries should be directed to R. M. Lambrecht. ety of operating conditions, in order that a t Research performed at Brookhaven National given facility can decide which production Laboratory under contract with the U.S. Energy Research and Development Administration, and method and irradiation conditions to use. The 12aTe(p, 2n)123I reaction was suggested ~z) partially supported by NIH Grant No 5. P41 in 1962. The early reports (16'2s'26) of RR00657. 395
396
K. Kondo, R. M. Lambrecht and A. P. Wolf
the high production yield encouraged examination of the production method. Based on our results ~16) at 28 MeV, a request
COLLIMATOR ( 5/B inch)
r+ V A V / / / / / / / ~ A A
.PERMANENT MAGNETS . r ~ ( ~ tOOOG see inserf below) .......
~ V///Z/'7///A I OTON BEAM
~
.... I
E223 E223 1.4//A.~/////////A NYLON ~ 1 I N SULATORS ~ TO EARTH
I
/ AI WINDOW
AXIS
1 T TO CURRENT INTEGRATOR
PROTON
PROTON BEAM
___
AI ~ " ~
~
POLYSTYRENE -/ Te FILM
Cu
FIG. 1. Experimental arrangement for measurements of excitation functions on the BNL 60 in. cyclotron.
EXPERIMENTAL M e a s u r e m e n t o f excitation functions
Isotopic enrichments of a24Te to 91.86% and 99.87% were purchased from Isotope Sales at O a k Ridge National L a b o r a t o r y at a cost of $1.75/mg and $15.00/mg, respectively. The percentage composition of Te isotopes in each e m i c h m e n t are listed in Table 1. The excitation functions were determined by the method of stacked, thin targets. Each target consisted of 1.05 + 0 . 0 1 mg T e / c m 2 uniformly suspended in a self-supporting polystyrene film. (31) TABLE 1. Isotopic composition of enriched 124Te % Isotopic enrichment* 91.86% 99.87%
12°Te
< 0.02
lZ2Te
0.49 0.11 91.86 3.17 1.81 1.55 1.05
123Te 124Te 125Te
126Te 128Te 13°Te
< 0.002 < 0.003 0.006 99.87 0.095 0.020 <0.010 < 0.008
* As reported by ORNL.
The powdered 124Te ( - 1 . 2 g) was uniformly suspended in 1.67 g of polystyrene and 23.9 ml of benzene. The solution was quickly
poured onto a clean, flat, Pyrex plate and allowed to dry at r o o m t e m p e r a t u r e for 1 hr. The advantages of the method is that a n u m b e r of uniformly thin Te targets can be conveniently prepared. The enriched 124Te is easily recovered as the support only contains C and H. The disadvantage is the poor thermal conductivity of the target which necessitates using a low intensity, diffused b e a m for the b o m b a r d m e n t s . The Te concentration in each target was determined at the conclusion of the experiment by dissolution in conc HNO3 and 72% HC104, and X-ray fluorescence spectrometry. The thin targets were stacked between A1 and Cu foils as b e a m degraders. The energy loss was calculated. (32) All irradiations were p e r f o r m e d on the B N L 60 in. cyclotron. The uncertainty in the incident proton b e a m energy was estimated as 1%. A highly defocussed, diffused and collimated proton b e a m was used for all measurements. The integrated b e a m was measured with a Faraday Cup in which a crossed 1 k G magnetic field was used to suppress secondary electrons. (See Fig. 1.) Cu foil monitors (12.57 mg/cm 2) employing the 63Cu(p, n)63Zn cross sections reported by COLLE e t a / . (33) gave an integrated flux which agreed within 1% of the value obtained with the Faraday Cup. The typical irradiation condition was 0.5 txA for 200 sec. The reaction cross sections were calculated by the usual method.
397
Iodine-123 production for radiopharmaceuticals-XX Non-destructive
measurements
2. Cross sections for the 124Te(p,2n)? and 124Te(p, E)‘*~I reactions on 99.87% isotopic
TABLE
After the bombardment each target was enrichment “‘Te mounted in a calibrated geometry in front of a 123 124 high-resolution Ge(Li) detector calibrated for I I efficiency with National Bureau of Standards u (mbarn) u (mbarn) sources. The distinct y-lines and half-lives were sufficiently distinguishable without 436.2rt34.9 43.7izl1.4 28.19kO.30 34.9k6.8 649.8 ~~68.8 chemical separation. To minimize systematic 26.43 f 0.34 37.3 zt 15.6 1017.9* 107 25.3610934 errors a Northern Scientific 4096 channel 30.5 f 8.2 914.4k45.7 24.10zt0.37 analyzer with 2-point digital stabilization was 53.815.8 1011.4zk59.6 22.65 *to.40 used. The dead-time losses were always less 889.6~69.5 65.6*4.0 20.86*0.41 than 10%. 84.8+ 13.9 630.9 It 70.5 18.82kO.45 The principal photopeaks of each nuclide 194.9 f 16.2 427.7kSl.l 16.35 *0.70 were followed to establish the half life and 455.5 k29.6 160.6* 6.4 14.54~t 0.72 confirm the identity of the nuclide. The 308.9* 38.8 24.515.6 12.45 f 0.79 Brookhaven decay curve analysis program, 115.9* 18.8 9.95kl.10 CLSQ, and a modified version of the spectral analysis program, BRUTAL, were used for the data reduction. (34)The Nuclear Data(33’ 35) TABLE 3. Cross sections for the lz4Te(p, 2n)lz31 y-lines, and the (abundance) used are: lz31 and lz4Te(p, n)12’? reaction on 91.86% isotopic enrichment lz4Te (13.3 hr, 159 keV, 83%), lz41 (4.17 days, 603 keV, 67%), and “3Zn (38.0 min; 670 keV, ‘23 124 I I 8.47% and 962 keV, 6.68%). P (mbarn) u (mbarn) The counting error at the 95.5% confidence level for lz31 and “‘1 was less than 3%. The 99.5k 19.9 32.4zt7.8 29.181tO.29 greatest errors arise from the uncertainties in 392.3k51.0 29.12*0.29 43.6rt9.6 the irradiation parameters resulting from any 615.Ozk37.8 27.4OzkO.30 66.1 f 10.9 lack of uniformity in the tellurium thickness 1066.4+111..5 25.64 f 0.34 86.8 * 10.5 (<2%), and specifically from heterogeneous 843.5 f 70.2 25.62zt0.34 59.6zk8.3 1137.8k68.2 distribution, if any. Impuritjes present in the 24.5OzkO.37 74.4*5.9 1037.7zt 103.8 24.44 i 0.37 70.5 * 8.7 target other than Te were < 1%. Recoil losses 838.8+98.9 22.58izO.40 68.5 f 8.9 of 231 and lz41 from the polystyrene matrix 867.8zt91.1 22.38~0.40 63.9* 6.7 were very small and were neglected in com904.1 ~k45.2 21.34*0.30 87.7k7.2 puting the cross sections. Overall errors are 912.6zt 77.6 20.18?~0.41 117.0*14.0 typically of the order of 12%, although rela740.2 zk50.3 19.04*0.43 167.3 zt23.6 tive errors for comparative yields from the 615.4k67.7 17.74+0.55 180.7 + 17.0 various reactions would be considerably smal512.7~~65.4 17.42zk0.59 376.8 rt 26.4 ler, since systematic uncertainties in detector 515.3k41.2 16.22 ztO.70 445.6+ 33.4 efficiencies and nuclear decay properties 52.9zk 12.7 14.34zt0.72 440.6 f 24.2 would be removed. 53.7* 18.7 13.33 zto.75 419.1*33.9 12.20*0.80
RESULTS Excitation
AND
DISCUSSION
functions
The 124Te(p, 2n)‘231 and rz4Tefp, n)lz41 reaction cross sections were determined for incident proton energies of 28.19-9.95 MeV for lz4Te of 99.87% isotopic enrichment; and from 29.18 to 12.20 MeV on ‘24Te of 91.86% enrichment. The experimental results are presented in Tables 2 and 3 and Figs. 2 and 3,
5.8+x6.0
237.6 f 28.5
respectively. In general, the excitation functions exhibit the expected trends for (p, a) and (p, 2n) reactions on nuclides of intermediate mass. However, certain details require elaboration. The ‘24Te(p, 2n)‘231 reaction has a flat maximum cross section of about 1 barn in the range of 23.5-25.5 MeV. The (p, n) reaction has a maximum cross section of about
398
oZ
K. Kondo, R. M. Lambrecht and A. P. Wolf A salient point is that the total cross section for formation of 1241 is substantially reduced (by about a factor of - 2 in the optimum section of the excitation functions) if ultrahigh enrichment 124Te is used.
tO0
H
/ I0
9'86%
/
I 8
I I0
'24Te
"I
o 12~ ~
I 12
I _1 I t [ I 14 16 18 20 22 24 PROTON ENERGY, MeV
Production yields and radionuclidic purity
j
I 26
i
I 28
IJ 50
_FIG. 2. Excitation functions for 123I and 1241by proton irradiation of 124Te of 91.86% isotopic enrichment. 450 mbarn at about 14.5 MeV. It is important to note the differences in the shapes of the excitation functions (cf. Figs. 2 and 3) with 124Te of 99.87% and 91.86% enrichment. The appearance of structure in the excitation functions at incident proton energies greater than 18 MeV is more evident with 91.86% enrichment XEgTe. The total cross section leading to 123I via the 123Te(p, n)123I reaction is estimated as -<1% for either enrichment of 124Te. However, the 91.86% 124Te contains 3.17% 125Te (Table 1). The 125Te(p, 3n)~23I 125Te(p, 2n)X24I reactions are likely making an appreciable contribution to the yield of 123I at Ep > 2 5 MeV, and the yield of 1241 at Ep > 16.5 MeV. [-
I
[
F
T
99.87%
Ioo0~
i-"-
]
I - - T ~ - - T
I
I -]
i24Te
° '23z 124 I
~ ~o0
~
o
_ 4
IO&
IC-
q
12
I
14
[
I
I
16 ll8 20 22 214 PROTON ENERGY, MeV
I
26
k
28
~
50
Fio. 3. Excitation functions for 123I and 1241by proton irradiation of t24Te of 99.87% isotopic enrichment.
Absolute cross-section measurements for the 124Te(p, 2n)123I reaction have not been previously reported. However scattered data have appeared concerning various aspects of the production rates and the resulting radionuclidic purity (see Table 4 and Fig. 4). Figure 4 depicts the production rates as a function of the proton energy on our targets of 91.86% enrichment 124Te. The yields, expressed as mCi/tzAhr, were calculated using the cross section data reported in Table 3, and assuming a target thickness of 1.0 MeV irradiated at a fluence of 1.0/xA for 1.0 hr. For comparison the production rates reported by ACERBI e t al. (2°) are also presented. It is apparent that the yield data of the two groups are in general agreement (but the BNL data are lower) if the energy axis is translocated to the right for the University of Milan data. T h e ~ r o d u c t i o n yields integrated over various 12 Te target thickness are compared in Table 4. Several discrepancies occur. The differences are probably attributable to the isotopic enrichment of the 124Te targets, the target thickness, uncertainties in the cyclotron proton energies, and in one case (26) a large uncertainty in detector efficiency calibrations. It is unfortunate that many papers published on isotope production for radiopharmaceutical applications do not report the nuclear data which was used. However, the production data in Table 4 can be summarized if we neglect the effects of isotropic enrichment. At 25 MeV with 415-420 mg/cm 2 targets, production yields of 14.7, 24.3, and 17.5 mCi//xAhr are reported by DEGLUME eta/., (25) ACERBI et al. (2°) and this work, respectively. For 256 mg/cm 2 targets at incident proton energies of - 2 7 and 25.8 MeV, the production rates reported by BEAVER(28' 29) and this work are comparable at -->10 mCi/txAhr. There is a serious disagreement in the expected and obtained yields of CAUWE et a/. (26),
399
Iodine-123 production for radiopharmaceuticals-XX
TABLE4. A comparison of production yield and radionuclidic purity data reported for the ‘24Te(p, 2n)IZ31 reaction under a variety of production
Reference (16) (2.5) (28,29) iz”:; This work
Production rate mCi/FAhr
conditions
Ep (MeV) incident
Target thickness m&m2
‘24Te (%) enrichment
27.8 25 30 27’“’
19.6 420 910 22.5
96.2 95 95 96.21
0.54 14.7 25.0 Z 10.(Yd’
0.5’“’ ib) (b1 0 78’“’
25 30 28 25.8 27 26 2.5 28
415 900 930 256 519 346 415 912
91.86 93.4 91.86 99.87 99.87 91.86 91.86 91.86
25(40)“’ 24.3 45 10.6 20.4 14.9 17.5 33.6
(bj 0.72 0.88 0.54 0.62 1.0 1.11 -
Radionytlidic 124I I 0 01
-1 0.0011 -
ptn$y at EOB 130 I I o.o? 1 0.0014 -
1 0.03 1 -
w Typographical error occurred in Table 2 of ref. 16 and reported the level as 0.05%. (U lz41 reported as l&2.4% radiotoxicity relative to pure I3 I. “) Actual proton energy entering the lz4Te c 27 MeV. w Routinely produce 2200 mCi/hr with a 20 &A ffuence. w Based on assay of 50 routine production lots. (f)The authors state “The accuracy of the yield figures is about 25% resulting mainly from the inaccurate knowledge of the target thickness, the error on the current measurement and on the efficiency calibration of the GeLi detector.”
I/
I)
PROTON
‘*‘I
ACERBl
n ‘?
THIS
‘
ACERBI
lz41
ENERGY
etol. WORK
i
MeV thickness irradiated with 28 MeV protons, the production rate reported by ACERBI et ~1.~~‘)was 45 mCi/pAhr; whereas we report 33.6 mCi/pAhr. However, DEGLUMEet uL(~~) reported a production rate of 25.0 mCi/pAhr for 30 MeV proton irradiation of 910 mgicm’ targets.
et al.
(MeV!
FIG. 4. A comparison of the production rates of 123I and I“‘1 on ‘24Te of 91.86% isotopic enrichment as reported by ACERBIet al. (ref. 20) and obtained in this work.
cf. 2.5 mCi/~Ahr and 40 mCi/pAhr, respectively, for 30 MeV proton on 900 mg/cm’ of f24Te enriched to 93.4%. With targets of - 11
The highest quality 1231, that is obtainable by a route alternate to the ‘23Xe-+1231 generator, is via the ‘24Te(p, 2n)1231 reaction lz4Te of ultrahigh isotopic enrichment The Gization of 99.9% vs. 91.8% 124Te incrkases the radionuclidic purity relative to 124I by a factor of nearly 2. Various data reported by other laboratories (see Table 4) clearly support this conclusion. We routinely use 99.87% 12*Te and an incident proton energy of 25.8 MeV on targets consisting of 80-256 mg/cm ’ ‘24Te with 3 hr irradiations at a ffuence of 10-15 @A (our maximum current available) to produce lz31 with <0.65% 1241at
I(. Kmdo,
400 R fmg 894
18
20
1048 /
22
PROTOW
R. M. ~u~~rec~t and A. P. Wolf
Te/cm*) 1212 /
1385 I
24
26
1567 I
28
ENERGY,MeV
FIG. 5.
Influence of incident proton energy, target compositio’n, target thickness and time on the radionuclidic quality of lz31. the time of use. The other radionu~lidic $purities present are lZ51 (1.1 X 10s3%), I (1.4x 1K3%) and 13’1 (3.1 x lo-“%). Within the limits of detection (~10-~%) 13’1 was absent. Figure 5 summarizes the optimum conditions we have determined for the production of lz31 via the 124Te(p, 2n)lz31 reaction with lz4Te of 99.87% and 91.86% enrichment. The results are given fqr short irradiation conditions. The per cent lz41 relative to ‘*? at the end of bombardment is given on the left side of Fig. 5 for various incident proton energies. The range of protons in Te is given on the top of the figure. The right side of Fig. 5 depicts a time scale which can be used to read the level of lz41 which arises as a function of time following the irradiation. It is clearly evident that by using ultra-high enrichment 24Te the radionuclidic purity at the end of production is enhanced by a factor of 2. The upper 1eve11F3n I the per cent lz41 that is acceptable in a radiopharmaceutical depends somewhat on the diagnostic use. For example, in terms of radiation dose delivered to the patient, a few per cent lZRI in ‘231-ortho-iodohippuran (a
renal agent) delivers a lower radiation dose, than does the same amount of lz41 in 1231iodide for thyroid scans. A second factor is the effect of the higher energy photons of 1241 (511, 604 keV) on the degradation of the scintiphotos. For many radiopharmaceutical applications, not requiring ultra-pure Y, it has been considered that about 5% Iz41 is acceptable!“@ 37f Therefore utilization of a 256 mglcm’ target of 99.87% IZ4Te at an incident proton energy of 25.8 MeV will result in lz31 with a shelf-life of >40 hr. The lz4Te(p, 2n)? reaction, while second best in radionuclidic purity to the 1*3Xe-‘2”T generator, does result in a high production yield which is comparable in fact to the yield of the lZ71(p,58)“’ Xe+ lZ31 generator. Utilization of the optimum production conditions on a target of ultra-high isotopic enrichment lz4Te is a promising and acceptable route to providing 231 for radiopharmaceutical applications. REFERENCES 1. LAMBRECHT R. M. and WOLE‘ A. P. Radiat. Res. 52, 32 (1972). 2. MYERS W. G. and ANGER H. 0. J. rztrcl. Med. 3, 183 (1962). 3. MYERS W. G. In Recent Ad~unces in Nuclear Medicine (Edited by LAWRENCE J. H.), pp. 131-160. Grune & Stratton, New York (1974). 4. WELLMAN I-I. N. and ANGER R. T., JR. Seminars in Nucl. Med. 1, 356 (1971). J. F., LAhloREcHr R. 5. ATKINS H. L., KLLWPER M. and WOLF A. P. Am. J. R(~~~~tge~~i., Radial. Therapy nucl. Med. 117, 195 (3973). 6. SODD V. J., BLUE J. W. and WELLMAN H. N. CIyclotron production of ‘23I. An evaluation of the nuclear reactions which produce this isotope. ~~~~M~E 70-4. 38 pp. U.S. Dept. of Health, Education and Welfare (October 1970). 7. BLUE J. W. and SODD V. J. In Uses of Cyclotrons in Chemistry, Metallurgy und Biolagy (Edited by AMPHLETT C. B.) pp. 138-147. 3utterworths, London (1970). C., REDVANLY s. LAMBRECHTR. M., MANTESCU C. S. and WOLF A. P. I. nud. Med. 13, 266 (1967). 9. LINDNERL., BRINK~~ANG. A., SUER T. H. G., SCHXMMELA., VIXNBOI~.RJ. TH., KARTEN F. H. S., V~SSER J. and LEURS C. J. in Rudi~p~ar~aceuticals and labeled Co~~~u~ds Vol. 1. pp. 308-316. Vienna, IAEA (1973).
Iodine-123 production for radiopharmaceuticals--XX 10. STANG L. G., JR., HILLMAN M. and LEBOWITZ E. The Production of Radioisotopes by Spallation. B N L Report 50195, T-547 (1969). 11. F v s c o M. A., PEEK N. F., JUNGERMAN J. A., ZIELINSKI F. W., DENARDO S. J. and DENARDO G. L. J. nucl. Med. 13, 729 (1972). 12. WEINREICH R., SCHULT O. and STOCKLIN G. Int. J. appl. Radiat. Isotopes 25, 535 (1974). 13. LEBOWtTZ E., GREENE M. W. and RICHARDS P. Int. J. appl. Radiat. Isotopes 22, 489 (1971). 14. LOBER~ M. D., PHELPS M. E. and WELCH M. J. J. nucl. Med. 14, 733 (1973). 15. GUILLAUME M., LAMBRECHT R. M. and WOLF A. P. Int. J. appl. Radiat. Isotopes 26, 703 (1975). 16. LAMBRECHT R. M. and WOLF A. P. In Radiopharmaceuticals and Labeled Compounds Vol. 1, pp. 275-290. Vienna, I A E A (1973). 17. LAMBRECHT R. M. and WOLF A. P. Int. Symp. of Radiopharmaceuticals, Atlanta, Georgia, 11-15 February, 1974. In Radiopharmaceuticals (Edited by SUBRAMANIAN G., RHODES B. A., COOPER J. F. and SODD V. J.) pp. 111124. Society of Nuclear Medicine, New York (1974). 18. ACERBI E., BIRATrARI C., CASTIGLIONI M., RESMINI F., SPAVIERI I. and VILLA G., Production of 123I for medical purposes at the Milan A V F cyclotron. Paper presented at the 11th European Cyclotron Progress meeting, 29 May-1 June (1974). 19. SODD V. J. In Radiopharmaceuticals (Edited by SUBRAMANIANG., RHODES B. A., COOPER J. F. and SODD V. J.) pp. 125-133. Society of Nuclear Medicine, New York (1975). 20. ACERBI E., BIRATTARI C., CASTIGLIONI M. and RESMXNI F. Int. J. appl. Radiat. Isotopes 26, 741 (1975). 21. ACERBI E., BIRATTARI C., CASTIGLIONI M., RESMINI F. and SPAWERI G. Nederlands Tijdschrift Voor Natuurkunde 22, 332 (1973). 22. RHODES G. A., WAONER H. N., JR. and GERRARD M. Isot. Radiat. Technol. 4, 275 (1967). 23. HUPF H. B., ELDRIDGE J. S. and BEAVER J. E. Int. J. appl. Radiat. Isotopes 19, 345 (1968). 24. SILVESTER D. J., SUYDEN J. and WATSON I. A.
401
Radiochem. Radioanal. Lett. 2, 17 (!969). 25. DEGLUME C., DEUTSCH J. P., FAVART D. and PRIEELS R. Int. J. appl. Radiat. Isotopes 24, 291 (1973). 26. CAUWE F., FEUTSCH J. P., FAVART D., PRIEELS R. and COGNEAU M. Int. J. appl. Radiat. Isotopes 25, 187 (1974). 27. LAMBRECHT R. M and DAvis W. C. Private communication (1973). 28. BEAVER J. E. In Proc. Conf. Thyroid and Endocrine System Investigations with Radionuclides, Miami Beach, Florida, (March, 1974) (to be published). 29. BEAVER J. In Proceedings of a meeting on Iodine-123 Applications in Nuclear Medicine, H E W Publication (FDA) 76-8033, pp. 48-49, 98-102. Bureau of Radiological Health (May 1975). 30. LAMBRECHT R. M., KONDO K. and WOLF A. P. In Proceedings of a meeting on Iodine-123 Applications in Nuclear Medicine. H E W Publications (FDA) 76-8033, pp. 86-91. Bureau of Radiological Health (May 1975). 31. WALL N. S. and IRVINE J. W. Rev. Sci. Instr. 24, 1146 (1953). 32. WILLIAMSON C. F., BouJoT J. P. and PICARD J. Rapport CEA-R-3042 (1966). 33. COLLE R., KISHORE K. and CUMMING J. B. Phys. Rev. C 9, 1819 (1974). 34. (a)CUMMING J. B. National Academy of Sciences-National Research Council. Nuclear Science Series Report No. NAS-NS-3107, 1962 (unpublished). (b) GUNNINK R., LEVY H. B. and NIDAY J. B. University of California Radiation Laboratory Report No. UCID-15140 (unpublished); modified by B. Erdal (unpublished). 35. AUBLE R. L. Nuclear Data Sheets B7, 363, 465 (1972). 36. PARAS P. Overview of Alternatives to 131I Use for Thyroid Diagnosis. Report, Bureau of Radiological Health, Rockville, Md. 20852 available on request. 37. DAHL J. R. and TILBURY R. S. Int. J. appl. Radial. Isotopes 23, 431 (1972).