Recent developments in the production of 18F, 75,76,77Br and 123I

0883-2889/86 $3.00+ 0.00 Pergamon Journals Ltd

Appl. Radiat. lsot. Vol. 37, No. 8, pp. 803-810, 1986 Int. J. Radiat. AppL Instrum. Part A

Printed in Great Britain

PROCEEDINGS OF THE INTERNATIONAL S Y M P O S I U M ON RADIOHALOGENS

NWTEI) eAPEaS Recent D e v e l o p m e n t s in the Production

of lSF, 75'76'77Br and 123I S. M. Q A I M Institut ffir Chemie 1 (Nuklearchemie), Kernforschungsanlage Jfilich GmbH, D-5170 Jfilich, F.R.G. Halogens are particularly useful for labelling biomolecules which find application in functional imaging using PET (e.g. with lSF, 75Br) or SPECT (with 123I). This paper reviews some of the recent developments in the production of ~SF,7SBr, 76Br, 77Brand mI. Nuclear data, thick target yields, advances in targetry and radiochemical separation methods, as well as radionuclidic impurities are discussed. Wherever possible a critical comparison of the various production routes is given. An evaluation of the possibility of production of the above mentioned radiohalogens using small cyclotrons is presented.

Introduction Of all the neutron deficient radioisotopes of halogens, ISF (tt/2 = 110 min) and 123I(tl/2 = 13.2 h) have found wide applications in diagnostic nuclear medicine, the former having almost ideal nuclear properties for positron emission tomography (PET) and the latter for single photon emission tomography (SPECT). Extensive studies on the production of these two radioisotopes have been performed over the years [for a recent review cf. Ref. (1)] and hundreds of millicuries of both these radioisotopes are now readily available. The neutron deficient radioisotopes of bromine, especially 75'76'77Br, o n the other hand, have not found the same broad applications, either due to their non-availability in large quantities or due to nonideal nuclear properties. 75Br is the most useful radioLsotope of bromine, having a convenient half-life it~/2 = 98 min), high fl+ emission rate (75.5%), and a "easonable positron energy (1.74 MeV). It has, how:ver, two disadvantages: firstly, the 286keV y-line lssociated with its decay gives rise to random coincilences (which can be avoided in modern time-of:tight tomographs) and secondly, the long-lived ,laughter 75Se as well as the associated 76Br-impurity increase the radiation dose to the patient. The radioisotope 76Br (tt/2 = 16.1 h) has a high positron energy (3.9 MeV) and a low fl + emission rate (57%), leading Io a considerably higher dose to the patient. Neverl heless, this radioisotope seems to be suitable for PET ,tudies on animals, especially baboons. The radioi~otope 77Br (tl/2 = 56h) decays predominantly by electron capture (99.3%) and emits y-rays of energies

239 keV (23%) and 521 keV (22%). It is more suitable for longer lasting studies. Its 52l keV y-line, however, is not suitable for conventional y-cameras and requires high-energy collimation. The production methods for 75Br and 77Br have also been recently reviewed.") In this paper we limit ourselves to a brief account of some of the new developments in this field of study, and present an evaluation of the possibility of production of the five above mentioned radioisotopes of halogens using small cyclotrons.

Fluorine-18

The two major processes for the production of JSF, viz. t~O(p, n) tSF and 2°Ne(d, ~) ~SF, applied in recent years are given in Table 1. Both of them can be used with low energy cyclotrons. In general, two types of target systems have been used: in the case of Ne, gas targets are used and for ~sO water targets have been employed. The Ne gas target is very useful for anhydrous precursor preparation. ~SF is obtained either as ~SFlabelled F 2 or as H~SF when F 2 or H2, respectively, is added. F 2 and its secondary precursors such as acetylhypofiuorite and XeF 2 are used as medium specific activity electrophilic precursors. Detailed studies on the characterization of conditions of tSF-labelled F2 production were performed at Brookhaven National Laboratory (BNL) ~22~and the method is now in routine use in many laboratories. The removal yield of [~SF]F2 is a function of target pressure and carrier concentration, increasing with increasing target pressure and decreasing with decreasing carrier concentration. The widest use of Invited paper presented at the International Symposium [28F]F2 and its secondary electrophiles has been so far in the synthesis of [~SF]2-FDG. c n Radiohalogens, Banff, Canada, September 1985. 803

804

S . M . QAlM Table 1. Common methods for the production of ~SF

Nuclear reaction ~80(p, n)tSF 2°Ne(d, ~)I~F

Energy range (MeV) 16 ~ 3 11 --*3 14~2 8~2

Theoretical thick target yield (mCi//a Ah) 80 "~ 60 J 28 ~ 17 f

If the gas mixture used as target material is Ne/H2 the product is HISF. However, reproducible and nearly quantitative recoveries of H18F are difficult to obtain. Considerable success has been achieved in recent years in the use of the ~80(p, n) ~8F reaction (4) for production purposes. Design studies <5'6)and construction of H~80 targets [cf. for example Refs (7-10)] have demonstrated that this reaction can easily lead to curie amounts of ~SFaq. At BNL, 17) for example, 0.6 mL H~80 is placed in a chamber (2 cm q~ x 0.2 cm deep) in a copper body cooled with a jet of water (I°C, recirculated) and irradiated with 16.5MeV protons at 30/~A. Thereafter it is transferred through 30 m of 0.8 mm polyethylene tubing to the chemistry laboratory in 3 rain using a stream of pressurized helium. At St Louis, (8'9)on the other hand, a 1.2-3 mL target is used and both open and closed modes of operation are employed. In the open mode the gaseous products formed are allowed to escape from the target, though this results in some loss of H~80 as well as ~SF. In the closed mode the gaseous products are made to accumulate. This results in an increase in pressure which has to be vigilantly watched. In both the processes, at the end of irradiation H~80 containing radiofluorine is forced out of the target holder by pressure. Although the cost of H~80 is not very high, if JSF is produced frequently, it may be necessary to collect the irradiated H~80 samples, to purify and to reuse them. The water targets render ~SF as solvated fluoride ion which is rather unreactive. Furthermore, depending on the target material some cationic and radiolytic products are also present causing difficulties in the nucleophilic synthesis of labelled compounds [cf. for example Refs (8,9)] Two other systems have been reported to obtain ~SFaq. In one system m) a small volume stainless steel chamber containing a 10 mL glass test tube with a silvered interior is used. The ~802 target gas is admitted and irradiated at a beam current of 2 gA. The ~SF produced and deposited on the inner surface of the target liner is removed by rinsing with hot water. A maximum yield of 75 mCi ~8F~q has been reported and its use in labelling CH~SF demonstrated. In the second system developed at Jfilich°2) a Ne gas target is used. After irradiation with 14 MeV deuterons at 25 p A the inner walls of the target are washed with 4 mL of water and the 18F,q activity is collected. The

Target H~80 (> 99% enriched) Ne + F 2 Ne+H, Ne + H 2 (post irradiation target wash)

Chemical form ~SF~q [18F]F2 HI~F 18Faq

batch yield amounts up to 250 mCi. A novel method for the synthesis of [~SF]2-FDG in high yields was developed ~3) starting with this t~F2q. Although a small cyclotron is generally capable of producing sufficient quantities of 18F (cf. yield data given in Table 1), it is often misleading to extrapolate the theoretical thick target yield data to high current production conditions [for a detailed discussion cf. Ref. (14)]. The yield is not linearly related to the current, due to several factors, such as radiolysis, hot atom effects, wall effects, gas expansion, bubble formation in liquid targets, etc. A comparison of the theoretical and experimental yields of ~SF via the 180(p,n)lSF (water target) and 2°Ne(d,~)~SF (gas target) processes is given in Fig. 1. The theoretical yields have been calculated from the reported excitation functions, C4'~5'~6)and the experimental yields for 1 h bombardments were normalized from the data of Wolf and Fowler (~4)for beam currents of 25 ktA in the case of Ne gas targets and 15-25 p A in the case of an H~80 target. Evidently, in a water target at low incident proton energies the experimental and theoretical yields do not deviate strongly; at high energies, however, the deviations become more pronounced. In a gas target, on the other hand, the deviations are significant at all the deuteron energies. Due to the resulting high practical yield of ~SF even at low incident proton energies, the use of H~80 targets has great potential for production purposes.

Bromine-75 For the production of this radioisotope several nuclear reactions have been suggested [for a recent review cf. Ref. (1)], out of which two processes, namely 75As (3He, 3n) 75Br and 76Se(p, 2n)75Br, have proved to be most suitable. The thick target yields of 75Br expected from those reactions are given in Fig. 2. The major impurity associated with both the processes is 76Br; its contributions under the optimum energy ranges are also given in Fig. 2. Evidently, the 76Se(p, 2n)75Br reaction is more advantageous provided that highly enriched target material is used. The 75As(3He, 3n)rSBr reaction, on the other hand, makes use of natural arsenic, and target technology has been well developed. Both the reactions demand a medium sized cyclotron. In both the cases solid targets are used and production is carried out in a batch process.

Production of ~SF, 75'76'77Br and 123I

805

!

102

Theoretical yield Theoretitol yield

..-t

o

/

--~101

C,oter ~ r ~ (gas forget)

g

2°Ne (d,O.) leF p.-

100

=

10

Ep

I

20

I

10

I

20

Ed

Incident porticle energy (MeV)

=

Fig. 1. Thick target yields of 18Ffrom 180(p, n) 18Fand Z°Ne(d,~t)~SFprocesses. The theoretical yields were calculated from the known excitation functionsC4'~5'~6)and the experimental yields were deduced from the data of Wolf and Fowler.(s4)

The 75As(3He, 3n)75Br reaction was investigated in detail at Jiilich [cf. Refs (17,18)]. A Cu3As-alloy was developed as high-current target material. Irradiations are done with 36 MeV3He-particle beams of about 100/~A in an internal target system. Radiobromine is separated from the irradiated target material via a high temperature thermochromatographic method (~950°C) and is taken up in 0.5 mL of hot water. Although the process is very reliable and has also been automated, its general drawback is the rather high level of 76Br-impurity (6-8% EOB). The 76Se(p, 2n)75Br reaction using enriched 76Se as target material was suggested by the Groningen group °9'2°) and a few selenides like AgzSe and Cu2Se were found to be suitable for irradiations with beam

103

,

currents ~<7 #A. The method has been recently investigated in detail at Jiilich3z~) An external rotating target system was developed using which it is possible to irradiate low melting materials like elemental 765e with 24 MeV proton beam currents up to 20 #A. A sketch of the system is given in Fig. 3. The target (76Se-metal on Al-plate) is coupled to a target holder which fits in a target head. The target is cooled at the back by ice-water (flow rate 10 L/min) and rotated during irradiation by pressurized air (up to 400 rotations/min). A defocussed collimated 24 MeV proton beam falls on the target at an angle of 19'~ and covers the whole 76Se-layer. The loss of 7 6 S e after a 1 h irradiation amounts to < 1%. The separation of radiobromine from irradiated 76Se is effected by ther-

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~Selp,2n) ~ r (96.5% enriched)

.,~ 10 z

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100

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~t~'- yield

~Br -impurity ,%,

~He

10" 15

I 20

t 25

36-,,.25 7.5 1.7 t J 30 35 incident particle energy (PleV)

40

Fig. 2. Thick target yields of 75Br calculated from the excitation functions measured at Jiilich.(2~,27)

S.M. QAIM

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Fig. 3. Sketch of the target, target holder and target head used at Jfilich (2t) for irradiations in a rotating system. The target consists of a thin layer of elemental 76Se on an Al-backing. The extracted proton beam is 0.2 cm out of centre and falls on the target at a grazing angle of 19°. m o c h r o m a t o g r a p h y at 300°C. A sketch of the apparatus used is shown in Fig. 4. Radiobromine is taken up in a small volume of hot water. The loss of 76Se during the process is ~ 1% and the target can be reused. The radiochemical yield of 75Br, however, is only ~ 4 0 % . The practical batch yields of 75Br achieved at Jiilich via both the 75As(3He, 3n)TSBr and 76Se(p, 2n)?SBr processes amount to about 200 mCi (EOB) and the levels of 76Br-impurity to about 6 and 3%, respectively. The yields from the latter process would be appreciably higher, and the 76Br-impurity lower, if higher energy protons would be used. Radiochromatographic analysis of the aqueous solution showed that in both the processes radiobromine ap-

Oven

Se layer

pears > 95% as 7SBr-. Atomic absorption and optical emission spectroscopy of the final products showed that no significant chemical impurities were present.

Bromine-76 Several methods for the production of this radioisotope have been reported but any critical review of those methods has so far not been presented. We give a summary of the various suggested processes (17'1s.2¢~29) in Table 2. In general the indirect method, viz. 76Kr--+76Br system, demands a high energy machine and the level of 77Br-impurity is rather high. Since so far only low or medium power density targets have been used, the batch yields

Condensation of

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Radiobromine )

Therrnocouple (300 *C )

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Fig. 4. Sketch of the quartz apparatus for dry distillation of radiobromine from 76Se-metal on Al-backing target.(2~)

Production of ISF, 75"76'77Br and

807

123I

Table 2. Methods for the production of 76Br

Nuclear reaction

Energy range (MeV)

Indirect method:

76Kr EC 76Br

Theoretical thick target yield of 76Br (mCi//zAh)

77Br-impurity (%)

Target

Typical batch yield (mCi)

Ref.

14.611

"~tBr(d, xn) 76Kr "tBr (p, xn)'t6Kr 76Se(3He, 3n) 7~Kr*

80 --* 55 65 ~ 50 36 --* 30

0.47 0.45 0.08

< 10 < 10 5

Direct methods: 75As(3He, 2n)76Br

18 --* 10

0.30

2.2

76Se(p, n)76Br*

16 ~ 10

8

0.15

77Se(p, 2n)76Br **

25 ~ 16

7.0

< I

NaBr KBr 76Se

3 <1 <1

Cu3As As 76Se Ag~6Se Sodium selenate

40 10 < 20 < 10 < 10

(22) (23, 25) (24,26) (17,18) . (29) (21 ) (20) (28)

* Using 96.5% enriched 76Se. ** Using 92.4% enriched 77Se.

achieved have been rather low. Out of the three direct methods of production, viz. 75As(3He,2n) 76Br, 76Se (p, n) 76Br and 77Se (p, 2 n ) 76Br, the latter two give the highest yields. However, any large scale production of 76Br using these two processes has not been demonstrated. Presently the method of choice is the 75As(3He, 2n)76Br reaction and is used at Jfilich and Orsay. At Jfilich the procedure used is the same as for 75Br (except for change in the energy range), and quantities up to 40 mCi are produced and used in animal experiments. At Orsay, on the other hand, an elemental As target is irradiated at medium currents (~ 10/~A) and radiobromine is separated by a wet ~hemical method/29) The batch yield is about 10 mCi and the radioisotope has found some applications in humans.

Iodine-123 The production and application of this radioisotope has been the subject of several conferences [cf. for example Refs (32-34)] and review articles/1'3°) In summary it may be mentioned that for its production about 25 nuclear processes have been suggested, all of which can be grouped under two general headings: (i) indirect methods, i.e. those which make use of the 123Xe~ 123I precursor system (ii) direct methods.

The ~23Xe~ t23Iprecursor method demands the use of medium to high energy machines and gives rise to high-purity 123I, the major impurity being 60 d ~25I (0.1-0.4%). For routine and large scale production the 127I(p,5n) 123Xe, 127I(d,6n) lZ3Xe and Cs, Broinine-77 La(p, spall)123Xe processes have been reported, Methods for the production of this radioisotope though the (p, 5n) reaction is most commonly used. aave been reviewed. 1,3° In contrast to the relatively The direct methods of production require low to arge number of publications dealing with cross- medium energy cyclotrons and in general consist of ~ections and low-current yield measurements, the proton and deuteron induced nuclear reactions on available information on high-current targets needed enriched tellurium isotopes. Out of the three major "or large scale production of 77Br is rather scanty. reactions, namely lZ4Te(p, 2n)1231, 123Te(p, n)123I and Recent advances in targetry and chemical processing 122Te(d,n)t23I, the (p, 2n) reaction has been most !rove been reported from Jfilich t17,18)and Los Alamos extensively investigated. It is a high-yield reaction but [cf. Ref. (31)], making use of the 75As(~t, 2n)77Br and the level of the ~24I-impurity precludes its wide-spread 'atMo(p, spall)77Br processes, respectively. The high- use for production purposes. In recent years the medical necessity for pure ~23I ~',urrent Cu3As-alloy target used for the production of SBr and 76Br is suitable for the production of 77Br has been emphasized and considerable efforts have ~,.lso. The only difference is that irradiations are been devoted to optimizing the known production arried out with 28 MeV or-particles (rather than with methods [of. Ref. (34)]. The (p, 5n) process has been -~He-particles). The batch yield of 77Br after its ther- extensively investigated at Davis [el. several convaochromatographic separation at 950°C amounts to tributions in Ref. (34)]. Excitation functions of the about 50 mCi (EOB); the radiobromine in aqueous 1271(p, xn)121-127Xereactions have been remeasured. 05) solution exists >95% as 77Br-. In the spallation The new data for the formation of 123Xe appear to process the radiobromine is separated by a wet agree with the Groningen data but not with the chemical method. The batch yield is about 300 mCi; Montreal and Harwell data. The discrepancy between the product exists as 77Br- and the radionuclidic the data is thus still not solved and a critical evalupurity is very high. It should be emphasized here that ation of all the reported excitation functions appears the relatively long half-life of 77Br combined with the mandatory. The optimum conditions for the proparasitic use of the beam renders the spallation duction of ~:3Xe via spallation have also been worked process for the production of 77Br very attractive. out (at TRIUMPF, LAMPF and SIN). Attempts to

808

S.M. QAI~

remove the 124I-impurity from the 124Te(p, 2n)t23I produced radioiodine via an isotope separator have so far met with only partial success and no breakthrough has been achieved. The ~22Te(d,n)123I process was investigated in detail at Jiilich C36) and Dresden337) The low yield of the process restricts its use to local production. Although the level of ~24Iimpurity is low, the product contains ~3°I-impurity. The effect of the latter impurity on the line spread function is not known. Some investigations on the 123Te(p, n)l~3I process were also performed [cf. contribution by H u p f in Ref. (34)] but no detailed study has been reported. The major recent development in the production of 1231 incorporates the use of the 123Xe(p, 2n) 123Cs /~ + ~ l~3Xe + 6 min

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12~Xe(p,2n)123Cs 12~Xe(p,pn)~Xe

10~ 15 .... 2'o .... 2'5 .... Proton energy (MeV)

124Xe(p, pn) 123Xe

Fig. 5. Excitation functions of t24Xe(p, 2n)~2SCs and t24Xe(p, pn) r23Xe reactions calculated using the precompound model. ~4°1

process. ~38'39) The 124Xe-content in natural xenon is only 0.10%; however, if highly enriched material is used as target, this process gives rise to very highpurity 123I. The excitation functions of the two contributing reactions have not been measured. A theoretical calculation ~4°) based on the precompound model, however, has been reported and is reproduced in Fig. 5. The Q-value of the 124Xe(p, 2n)123Cs reaction calculated from the newest mass tables is - 1 5 . 1 1 M e V . This value and the systematics of (p, 2n) reactions in this mass region tend to suggest that the theoretical curve in the region of its threshold is in error. Experimental yields obtained ~38)for on gas energies of ~<21 MeV are considerably lower than those calculated from the theoretical excitation function, supporting the above suspicion. It is expected that the optimum energy range for the process would lie between 25 and 30 MeV. Although so far the question of accurate nuclear data has not been addressed in detail, the production process has been technically developed at A E C L , C a n a d a and Kernforschungszentrum, Karlsruhe, G e r m a n y and curie amounts of high-purity 1:~3Iare now produced routinely. Enriched ~Z4Xebeing very expensive, highly sophisticated target technology is involved. At the

A E C L relatively long irradiations at high currents are performed and the radioiodine is separated in two steps, firstly via target wash and secondly, by transfer Of the irradiated gas to a glass vessel, followed by washing the walls after a suitable decay time. At the K f K Karlsruhe, on the other hand, only the second step is applied. The recovery yield of the radioiodine is higher in the Canadian process. However, the target wash fraction contains some 121Te impurity ( < 0 . 0 2 % ) . A comparison of the various parameters relevant to the production at the two laboratories is given in Table 3. It seems worthwhile to mention that the availability of ~24Xe in high enrichments offers the possibility of l:3I-production using fast neutrons. Recently an evaluation of the possibility of 123I-production via the 124Xe(n, 2n)123Xe reaction was performed "1) and it was concluded that an intense neutron generator (thn~5 × 101:cm-2s-% such as at Livermore) can yield up to 100mCi of high-purity 123I, if > 9 9 % enriched ~24Xe is used as target material. The information available on the commonly used production methods of 1231is summarized in Table 4. The radionuclidic composition of radioiodine is given at 30 h after EOB, since this appears to be a realistic

Table 3. Production of ~23Iusing 124Xe as target material* KfK Karlsruhe Parameter AECL, Canada Germany Target material** 124Xegas (99.9%) ~24Xegas (99.9%) Size of target 2cm ~b x 30cm 1.2cm tk × 25cm Pressure (bar) 2 7 Energy range (MeV) 27 ~ 25 30 ~ 25 ~23I-yield(mCi//JAh) 4.2 ~ I0 Beam current (#A) 100 30 Irradiation time (h) 9 4 Cooling time (h) 3 7 Batch size (Ci) 3 1-4 '2sI-impurity at end of processing (%) <0.001 <0.001 Other impurities at 24 h after EOB (%) Not detected*** Not detected * The reaction t24Xe(n,2n) 123Xe can lead up to 100 mCi ~231using 99% enriched )24Xeand an intense 14 MeV neutron generator (cf. Ref. (41)]. ** Cost of gas/litre in U.S.$200000; one target filling costs about $50000. *** In target wash samples some ~21Te(<0.02%) was detected.

Production of ~SF, 7x76'77Brand ~2Jl

809

Table 4. Radionuclidic composition of radioiodine produced via commonly used processes (30 h EOB) Optimum particle Target Thick Radionuclidic content (%) energy range enrichment targetyield 1231 1241 12~I 1261 1301 ~3~I Reaction (MeV) (%) (mCi/#Ah) Indirect 127I(p,5n) 65 ~ 50 Natural 15 99.3 w 0.7 124Xe(p,2n) } ~23Cs~ ~23Xe 124Xe(p, pn)t2JXe Direct ]24Te(p,2n) 123Te(p,n) ~22Te(d, n)

30-~25

99.9

26 ---,23 15 ~ 10 16 ~ 8

96.5 91.5 96.5

~10

10 3.2 2.0

>99.99

96.2 98.3 97.5

--

<0.01

3.8

.

1.7 0.4

---

.

.

? 0.3

.

? 1.4

? 0.4

Table 5. Evaluation of production of radiohalogens using small cyclotrons* Two particle cyclotron Single particle cyclotron (Ep ~ 10 MeV) (E0 = 16 MeV; Ed = 8 MeV) Theoretical thick Theoretical thick target yield target yield Process (mCi/#Ah) Process (mCi//zAh) Radioisotope ]8F ISO(p, n)ISF 80 ~SO(p,n) ISF 50 2°Ne(d, ~)lSF** 17 75Br 7SKr(p, ~)75Br I 7SKr(p, ~)7~Br <0.1 76Br 76Se(p, n) 76Br 8 768e(p, n) 76Br I 77Se(p, 2n) 7~Br I 775e(p, n) 77Br < 0.2 77Br 77Se(p, n) 77Br 1.5 7SSe(p, 2n)77Br 0.2 123I ~23Te(p, n)1:31 3.5 123Te(p,n)]~3I 0. I ~2Te(d, n)t:3I <0.2 124Xe(p, x) 123Xe-* 123I < 0.2 * Using highly enriched isotopes as target material, unless otherwise stated. ** No enrichment of target needed.

ime for performing various steps like separation, abelling, quality control, distribution and medical ;tpplication. Evidently, the J24Xe(p, 2n) J23Cs--* 23Xe--t-|24Xe(p, pn)J23Xe process gives the highest purity 123I reported so far. Notwithstanding the technological problems associated with the highly expensive ~24Xe-target material, the use of this process is recommended provided a high intensity 30 MeV l,roton beam is available.

Evaluation of Production of Radiohalogens using Small Cyclotrons In recent years there has been considerable interest whether a small cyclotron has the capability of producing (besides the short-lived fl + emitters) some rtdiohalogens in quality and quantity suitable for n ledical applications. The theoretical yields of the five r.tdioisotopes of halogens under discussion are given ilt Table 5 for two types of small cyclotrons. Evidently, both two-particle and single-particle c/clotrons can lead to sufficient quantities of ~SF if (I', n) reaction on highly enriched ~sO is used. On the other hand, the laF-yield from the 2°Ne(d,~t)laF reaction over the energy range of 3 - 1 0 M e V is strongly dependent on the energy of the incident deuterons. If the loss of deuteron energy in the target window is appreciable, the ~8F-yield will be drastically reduced.

The radioisotopes 76Br, 77Br and 1231 can be produced in sufficient quantities via (p, n) reactions on highly enriched 765e, 775e and ~23Te, respectively at a 16 MeV proton cyclotron but not at a 10 MeV single particle cyclotron. For 75Br-production at a low energy cyclotron the 7SKr(p, ~)75Br reaction has been suggested. <421 The expected yield even from a highly enriched 7SKr target is low and batch yields > 30 mCi would be difficult to achieve. Due to the low yield and the high cost of the enriched 7SKr gas (one target filling would cost about $23,000), this process is not recommended. The production of 75Br is best performed via the 75As(3He, 3n)75Br or 76Se(p, 2n)75Br reaction, and a medium sized cyclotron is essential. Similarly, the 124Xe(p, 2n)123Cs ~ 123Xe --F 124Xe(p, pn)123Xe process is expected to have negligibly low yield at 16 MeV. For using this method of production a medium sized cyclotron is needed. Note added in proof--After the completion of this review the author learned that besides AECL (Canada) and KfK Karlsruhe (Germany) a group in Eindhoven (Netherlands) has also been producing n3I for some time via the 124Xe(p,x)223I reaction using 99.8% enriched 124Xe. The yields and quality of ~23I achieved are similar to those reported from the other two laboratories. Acknowledgements--The author is highly indebted to Professor Dr G. St6cklin for stimulating discussions, constant support and encouragement, and a critical appraisal of this

810

S.M. QAIM

manuscript. Acknowledgement is made to colleagues who placed some of their published and unpublished data at the disposal of the author.

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