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Production of 52Fe for use in a radionuclide generator system
1TtchnicalRllte International
Journal of Nuclear Medicine and Biology Vol. 7. pp. 15 to 78
Pergamon PressLtd 1980. PrintedinGreatBritain
Production of 52Fe for Use in a Radionuclide Generator System* R. W.
ATCHER~,
A.
M.
FRIEDMANS
and
J., R.
HUIZENGA
Argonne National Laboratory, Argonne, IL 60439, U.S.A. and Department of Chemistry, University of Rochester, Rochester, New York, U.S.A. (Received 11 April 1979) 52Fe is the parent for a radionuclide generator system which separates the daughter activity, s2mMn, half-life 21.1 min. A variety of production schemes is available for s2Fe, half-life 8.3 h. The ease with which the parent can be made greatly enhances the potential of the generator system. Production by (3He, 3n), (4He, 2n), (p, 4n) and (p, spallation) reactions is discussed. 1. Introduction IRON-52 has been recognized as a good radionuclide for use in nuclear meaicine for a number of years.“-” Other radionuclides of iron do not have suitable halflife, decay characteristics for detection outside the body or radiation dosage for use in vim. In particular, iron tracers are useful for visualizing bone marrow and other metabolic processes using iron. “Fe has not been used extensively in nuclear medicine to date, primarily because it and its daughters decay by positron emission and its daughters emit high energy y-rays not easily detected by conventional two-dimensional imaging systems. Its half-life, 8.3 h, is relatively short for a cyclotron product to be used commonly in nuclear medicine. Commercial suppliers have not provided “Fe on a routine basis. The 169 keV y-ray emitted by s2Fe is not easily imaged in the Compton scatter from the daughters’ high energy y-rays. Recently, we have developed a generator system which separates s2mMn from s2Fe.‘4’ s2mMn has a short half-life, 21.1 min, and has shown potential as a myocardial imaging agent. s2Fe can be produced in curie quantities by reactions not used for s2Fe production for medical use since there is significant production of other iron radionuclides. * Research supported in part by the Of&e of Health and Environmental Research, U.S. Department of Energy. t Present address: Department of Radiology, Peter Brent Brigham Hospital, 721 Huntington Ave., Boston, MA 02115, U.S.A. t Address all correspondence to: Arnold Friedman, Chemistry Division, Argonne National Laboratory, Argonne, IL 60439, U.S.A.
The decay scheme is shown in Fig. 1. s2Fe decays by positron emission (56x, 0.80 MeV) and electron capture.“) Both decay modes deexcite through a 169 keV level in s2mMn, 100% abundance. Though not useful for imaging, the y-ray provides an easy method for breakthrough detection using a Ge(Li) spectrometer coupled to a multichannel analyzer. The daughter, 52mMn, decays by positron emission (98x, 1.63 MeV) and isomeric transition to “Mn, half-life 5.6 days. The high flux of 511 keV annihilation y-rays, 197x, makes the nuclide ideal for imaging in emission computed tomography which has been introduced in commercial machines recently. The daughter also emits a 1434keV y-ray. abundance lOOo/ s2Mn decays by electron capture, 66x, and emission of a positron, 0.575 MeV. It too emits a 1434 keV y-ray, lOO%, and many others, the strongest being 744 keV (90%) and 935 keV (94%). While its presence increases the radiation dosage, only 52 nCi are formed per 1 mCi’ SLmMn. A generator left overnight would have to be pre-eluted to remove the increased level of 52Mn before the generator product was used for diagnostic studies. 2. Experimental Methods and Results 2.1 4He reactions s2Fe can be produced using a number of nuclear reactions. The most likely to be used by an institution with an in-house cyclotron is by 4He or 3He bombardment of natural chromium. Natural chromium’s isotopic content is: 50,4.3%; 52, 83.8%; 53, 9.60/,: and 54, 2.4%. Originally, s2Fe was made using 4He bombardments of chromium. YANO and ANGER(~) used the reaction to demonstrate the production and chemical processing for medical use. They used a 65 MeV beam on a chromium powder target which had been pressed into a disc. This disc was enclosed in aluminum and irradiated with a 12 PA beam. They reported a yield of 8 &i/pAh per gram of chromium. Their separation scheme involved ether extractions from hydrochloric acid and took 6-7 h to produce a biologically compatible solution of ferrous citrate. The chemical yield is 99% if carrier iron is used. “Fe, produced by 52Cr(4He,n)sSFe, is about 5-67; of the s2Fe produced at end of bombardment (EOB). “Fe has a 2.9 y half-life and decays by electron capture producing 5.6 keV X-rays. THAKUR et al.“’ used the 30MeV 4He beam at Hammersmith Hospital to produce s2Fe using an internal target irradiated with a 500 gA current. They used chromium electroplated onto a copper backing which first had been electroplated with nickel. This highly conducting backing enabled them to bombard with high current without destroying the target or experiencing evaporation losses. The yield ‘is 3.3 &i/ fib, somewhat more than predicted by YANO. 5sFe was 14% of 52Fe (EOB):The chemical yield from processing the target was 100% and took 1.5 h. They point out that the ether extraction should be done
76
Technical Note
FIG. 1. from hot acid which enables them to operate without carrier iron. 2.2 3He reactions GREENEet al.@) used a 45.5 MeV 3He beam to produce “Fe by (3He,3n) on “Cr. The yield for this reaction was SO@i/pAh. Natural chromium was electroplated onto an internal target holder to a depth of 0.25 mm. The target was tilted to increase the effective thickness to 0.56mm. They also used an ether extraction to isolate the ‘*Fe. “Fe contamination is estimated to be O.OOl~Oat EOB. At Argonne National Laboratory, we use a 33 MeV 3He beam on an external target of natural chromium “Fe was plated on copper. (I) The yield is 20 &i/dh. measured to be less than 0.07% (EOB). The target is dissolved in concentrated hydrochloric acid, treated with concentrated nitric acid to ensure that all 52Fe is in the (III) oxidation state and the 52Fe is isolated on an anion exchange resin* in 8 N HCI. The chromium from the target and the manganese radionuclides produced are washed through the column in 8 N HCI. The ‘*Fe is stripped from the column in water at a yield of 9S_lOO%. MURUKAM~(~) did a comparative study and concluded that 3He is superior to 4He for production. Their data agreed with past studies on reaction yield at given energies. In fact, if 3He beam energy is increased from 30 to 40 MeV, ‘*Fe yield increases by a factor of four, whereas “Fe yield increases by 10%. They separate the iron by solvent extraction into diisopropyl ether, although no chemical yield data was given.
2.3 Proton reactions The medium energy proton beams available at Brookhaven Linac Isotope Producer (BLIP)(“) and the Los Alamos Meson Physics Facility (LAMPF)‘“’ provide a means to produce larger quantities of 52Fe. * Bio-Rad Ag 1 x 8.
These machines produce 52Fe by 55Mn@, 4n), or by spallation reactions on targets with 2 > 26. SAHA and FARRER(‘*)studied the (p,4n) reaction using 65 MeV protons on a manganese dioxide target irradiated at OS@ Typically, the irradiation lasted for 1 h and produced 80&i of activity, a yield of 160 @i/pAh. The “Fe was separated by dissolving the MnO, in HCl and eluting through an anion exchange column, stripping the column and repeating the resin step. The separation took 2 h and the chemical yield was 70--80%. They estimate 55Fe production at less than 3% of 52Fe (EOB). The linacs at LAMPF and BLIP produce protons for other uses, but have been equipped with isotope production facilities. These accelerators produce protons of 800 and 200MeV at currents of 300 and 70 PA, respectively. BLIP routinely produces 52Fe for medical use by irradiating a 2.5 g/cm2 manganese powder target. The proton.energy is degraded in the target from 70 MeV to 50 MeV. An irradiation at 70 fi for 15 h will produce 115 mCi of $*Fe (EOB). “Fe is less than 0.7% ‘*Fe levels at EOB. This contamination level is low enough to allow administration to patients. The final, production method is by spallation. A target of 2 higher than iron is irradiated in a beam higher than lOOMeV, typically. The incident proton knocks out a number of protons and neutrons. SODD et al.” 3, used targets of manganese cobalt, nickel and copper to measure ‘*Fe production from hydrochloric acid into ether. The cross section for the reaction with nickel is 1.35 mb, about a factor of 10 higher than for cobalt or copper. The targets were irradiated with an external beam and of 50nA and monitored by 24Na production in aluminum. “Fe yield is 3.3% (EOB) and 59Fe yield is 0.16%. Radiation dosage from 59Fe is high since it decays by &emission and emits several high energy y-rays and has a 45 day half-life. A trial spallation production run was done at BLIP.(r4i A 20mm nickel foil was irradiated by
17
Technical Note TABLE 1.
Reaction
Particle 3He
“He P
52Fe production reactions
Particle energy
52Cr(3He, 311) 52Cr(3He, 3n) 52Cr(3He, 3n) “°Cr(4He, 2n) 50Cr(4He, 2n) 5sMn(p, 4n) “Mn(p, 4n) Nib. spallation) Ni(p, spallation) Nib. spallation)
45.5 33 40 65 30 65 70 200 588 800
Thick target yield (KilpAh)
Reference
50 20 50 8 3.3 160 -110 61* 700t 3300t
(8) (1) (9) (6) (7) (12) (16) (16) (13) (14)
* Thin target yield. t Estimated from cross-section measurement.
200 MeV protons, degrading the beam about 1.5 MeV. A 15 h irradiation at 70 PA produced 70 mCi at EOB. The relative production of 55Fe and 59Fe was 2.0 and 0.15% respectively. Obviously, a thicker target would increase yield significantly. The foil was relatively impure and introduced a high stable iron content to the final product, which would inhibit the use of the 52Fe in a compact generator system. At LAMPF, the cross section for spallation on a nickel target was measured at 800 MeV at an integrated current of 1 PA. They report a value of 1.54 mb for “Fe and 0.306mb for 59Fe. The chemical yield for the separation is 96%.‘15) They project an 52Fe yield of 8.3 Ci at half-saturation, assuming a target thickness of 2.3 cm and a 300 pA current. Recently a stack of foils was irradiated and processed producing 1 Ci EOB after a 16 h irradiation!‘@ The intensity of the beam passing through,the target was not known, because the beam spot was larger than the 1 in. diameter targets. The target was processed, 52Fe isolated and delivered to the West Coast in 24 h.
3. Discussion The production of 52Fe for medical use’has, until this time, been done for injection into patients. The development of the generatorc4i has increased potential uses for the radionuclide. Simultaneously, the requirements for radionuclidic purity have changed as well as the quantities needed. The specific activity of the 52Fe is also a factor since the generator size is dictated by the amount of iron present. The current generator utilizes an anion exchange resin,* 10&200 mesh, in a column 2 mm (i.d.) by 40 mm. The resin is supported at the top and bottom by glass wool plugs. 52mMn is eluted in 8 N HCl at a yield of 75%. Breakthrough is one part in 10,ooO or less. The elution is complete in two column volumes, 0.25 ml. While the normality of the HCl is high, evap* Bio-Rad Ag 1 x 8. t Cyclotron Corporation.
oration and dissolution in an appropriate buffer can be done in a few minutes. Mn(II) has shown itself to be a promising myocardial imaging agent. “‘I Its rapid blood clearance and high myocardial concentration both indicate a shortlived manganese radionuclide would be ideally suited for this use. The short processing time is necessary to prevent decay losses. The production capabilities of the reactions are summarized in Table 1. The spallation reaction has the highest yield, obviously, and provides the best source of 52Fe for use in a generator system. The high level of 55Fe and 59Fe would be problematic if the 52Fe were to be injected directly, but not in a generator. A 100mCi generator would yield 2OOnCi of “Fe and 15 nCi of 59Fe or less per elution. The large targets required by these higher energy machines require longer workup times and greater volumes of reagents. It is imperative that these be extremely pure in order to hold levels of carrier iron to a minimum. Since the high current machines are capable of production by spallation, it would be unnecessary to produce 52Fe by bombarding manganese. For cyclotrons able to produce 70 MeV proton beams, the current is generally so low that production is better done using a 3He beam. Even relatively low energy machines could be used to produce 52Fe. A CS-15,t commonly found around the country, has an internal current of 3001_1Afor 3He. Even at its energy of 24 MeV, it is still able to produce 1.5 mCi/h, or 12 mCi in 8 h, enough for a generator of useful size. Even a 4He beam could be used since the high levels of 55Fe produced by 52Cr(4He,n), would be easily tolerated in a generator system. The threshold for the reaction, 15 MeV, would eliminate using a CS-15 which produces 4He at this energy. but would not preclude using other cyclotrons with a slightly higher energy. Production at low energy increases the “Fe contamination since the energy is nearer to the peak in the excitation function for the (‘He, n) reaction In summary, many production methods for s2Fe provide many sources of supply for the s2Fe-52mMn
Technical Note
18
LEDERERC. M. and SHIRLEYV. S. Table of ISOCopes,7th edn, p. 146. Wiley, New York (1978). YANOY. and ANGER H. 0. Int. J. uppl. Radiat.
generator. Production could be tailored to the needs of the generator user; multicurie generators could be produced for hospitals performing many procedures or small generators could be produced on a day to day basis using relatively small cyclotrons nearby.
Isotopes 16, I53 (1965).
THAKURM. L., NUNN A. D. and WATERSS. I,. Int. J. appl. Radiat. lsotopes 22, 481 (1971).
Acknowledgements-The
authors would like to thank Karen Knoerr for manuscript preparation. Research support is provided by the Office of Health and Environmental Research, U.S. Department of Energy. One of the authors (R.W.A.) would like to thank the Argonne Center for Educational Affairs for support during the course of this work.
References
8. GREENEM. W., LEBOWIT~E., RICHARDSP. et al. Int. J. appl. Radiat. Isotopes 21, 719 (1970).
9.
MURAKAMIY., AKIKA F. and EZAWA 0. Radiopharmaceuticals and Lahelled Compounds, p. 257.
IAEA, Vienna (1973). 10. SERAFINIA. N. and BEAVERJ. E. Medical Cyclotrons in Nuclear Medicine, p. 16. Karger, Base1 (1978). Il. Ibid., p. 34. 12. SAHA G. B. and FARRER P. A. Int. J. appl. Radiat. Isotopes 22, 495 (1971).
RAYUDUG. V. S., SHRAZI S. P. H., FORDHAM 13. SODD V. J., SCHOLZK. L. and BLUE J. W. Med. Phys. 1, 25 (1974). E. W. et al. int. J. appl. Radiat. Isotopes 24, 451 14. RICHARDSP. Private communication. (1973). 15. GRANT P. M., O’BRIENH. A., BAYHURSTB. P. et KNOPSEW. H., RAYUDIJG. V. S., CARDELLOM. al. Proc. 2nd Int. Symp. Radiopharmaceutical et al. Cancer 37, 1432 (1976). Chemistry, Oxford, England (1978). ANGERH. O., VAN DYKED. C. Science 144, 1587 16. O’BRIENH. A. Private communication. (1964). H. R., HALPERN ATCHERR. W., FRIEDMANA. M., HUIZENGAJ. R. 17. CHAUNCEYD. M., SCHELBERT S. E. et al. J. nucl. Med. 18, 933 (1977). et al. J. nucl. Med. In press.
Journal of Nuclear Medicine and Biology Vol. 7. pp. 15 to 78
Pergamon PressLtd 1980. PrintedinGreatBritain
Production of 52Fe for Use in a Radionuclide Generator System* R. W.
ATCHER~,
A.
M.
FRIEDMANS
and
J., R.
HUIZENGA
Argonne National Laboratory, Argonne, IL 60439, U.S.A. and Department of Chemistry, University of Rochester, Rochester, New York, U.S.A. (Received 11 April 1979) 52Fe is the parent for a radionuclide generator system which separates the daughter activity, s2mMn, half-life 21.1 min. A variety of production schemes is available for s2Fe, half-life 8.3 h. The ease with which the parent can be made greatly enhances the potential of the generator system. Production by (3He, 3n), (4He, 2n), (p, 4n) and (p, spallation) reactions is discussed. 1. Introduction IRON-52 has been recognized as a good radionuclide for use in nuclear meaicine for a number of years.“-” Other radionuclides of iron do not have suitable halflife, decay characteristics for detection outside the body or radiation dosage for use in vim. In particular, iron tracers are useful for visualizing bone marrow and other metabolic processes using iron. “Fe has not been used extensively in nuclear medicine to date, primarily because it and its daughters decay by positron emission and its daughters emit high energy y-rays not easily detected by conventional two-dimensional imaging systems. Its half-life, 8.3 h, is relatively short for a cyclotron product to be used commonly in nuclear medicine. Commercial suppliers have not provided “Fe on a routine basis. The 169 keV y-ray emitted by s2Fe is not easily imaged in the Compton scatter from the daughters’ high energy y-rays. Recently, we have developed a generator system which separates s2mMn from s2Fe.‘4’ s2mMn has a short half-life, 21.1 min, and has shown potential as a myocardial imaging agent. s2Fe can be produced in curie quantities by reactions not used for s2Fe production for medical use since there is significant production of other iron radionuclides. * Research supported in part by the Of&e of Health and Environmental Research, U.S. Department of Energy. t Present address: Department of Radiology, Peter Brent Brigham Hospital, 721 Huntington Ave., Boston, MA 02115, U.S.A. t Address all correspondence to: Arnold Friedman, Chemistry Division, Argonne National Laboratory, Argonne, IL 60439, U.S.A.
The decay scheme is shown in Fig. 1. s2Fe decays by positron emission (56x, 0.80 MeV) and electron capture.“) Both decay modes deexcite through a 169 keV level in s2mMn, 100% abundance. Though not useful for imaging, the y-ray provides an easy method for breakthrough detection using a Ge(Li) spectrometer coupled to a multichannel analyzer. The daughter, 52mMn, decays by positron emission (98x, 1.63 MeV) and isomeric transition to “Mn, half-life 5.6 days. The high flux of 511 keV annihilation y-rays, 197x, makes the nuclide ideal for imaging in emission computed tomography which has been introduced in commercial machines recently. The daughter also emits a 1434keV y-ray. abundance lOOo/ s2Mn decays by electron capture, 66x, and emission of a positron, 0.575 MeV. It too emits a 1434 keV y-ray, lOO%, and many others, the strongest being 744 keV (90%) and 935 keV (94%). While its presence increases the radiation dosage, only 52 nCi are formed per 1 mCi’ SLmMn. A generator left overnight would have to be pre-eluted to remove the increased level of 52Mn before the generator product was used for diagnostic studies. 2. Experimental Methods and Results 2.1 4He reactions s2Fe can be produced using a number of nuclear reactions. The most likely to be used by an institution with an in-house cyclotron is by 4He or 3He bombardment of natural chromium. Natural chromium’s isotopic content is: 50,4.3%; 52, 83.8%; 53, 9.60/,: and 54, 2.4%. Originally, s2Fe was made using 4He bombardments of chromium. YANO and ANGER(~) used the reaction to demonstrate the production and chemical processing for medical use. They used a 65 MeV beam on a chromium powder target which had been pressed into a disc. This disc was enclosed in aluminum and irradiated with a 12 PA beam. They reported a yield of 8 &i/pAh per gram of chromium. Their separation scheme involved ether extractions from hydrochloric acid and took 6-7 h to produce a biologically compatible solution of ferrous citrate. The chemical yield is 99% if carrier iron is used. “Fe, produced by 52Cr(4He,n)sSFe, is about 5-67; of the s2Fe produced at end of bombardment (EOB). “Fe has a 2.9 y half-life and decays by electron capture producing 5.6 keV X-rays. THAKUR et al.“’ used the 30MeV 4He beam at Hammersmith Hospital to produce s2Fe using an internal target irradiated with a 500 gA current. They used chromium electroplated onto a copper backing which first had been electroplated with nickel. This highly conducting backing enabled them to bombard with high current without destroying the target or experiencing evaporation losses. The yield ‘is 3.3 &i/ fib, somewhat more than predicted by YANO. 5sFe was 14% of 52Fe (EOB):The chemical yield from processing the target was 100% and took 1.5 h. They point out that the ether extraction should be done
76
Technical Note
FIG. 1. from hot acid which enables them to operate without carrier iron. 2.2 3He reactions GREENEet al.@) used a 45.5 MeV 3He beam to produce “Fe by (3He,3n) on “Cr. The yield for this reaction was SO@i/pAh. Natural chromium was electroplated onto an internal target holder to a depth of 0.25 mm. The target was tilted to increase the effective thickness to 0.56mm. They also used an ether extraction to isolate the ‘*Fe. “Fe contamination is estimated to be O.OOl~Oat EOB. At Argonne National Laboratory, we use a 33 MeV 3He beam on an external target of natural chromium “Fe was plated on copper. (I) The yield is 20 &i/dh. measured to be less than 0.07% (EOB). The target is dissolved in concentrated hydrochloric acid, treated with concentrated nitric acid to ensure that all 52Fe is in the (III) oxidation state and the 52Fe is isolated on an anion exchange resin* in 8 N HCI. The chromium from the target and the manganese radionuclides produced are washed through the column in 8 N HCI. The ‘*Fe is stripped from the column in water at a yield of 9S_lOO%. MURUKAM~(~) did a comparative study and concluded that 3He is superior to 4He for production. Their data agreed with past studies on reaction yield at given energies. In fact, if 3He beam energy is increased from 30 to 40 MeV, ‘*Fe yield increases by a factor of four, whereas “Fe yield increases by 10%. They separate the iron by solvent extraction into diisopropyl ether, although no chemical yield data was given.
2.3 Proton reactions The medium energy proton beams available at Brookhaven Linac Isotope Producer (BLIP)(“) and the Los Alamos Meson Physics Facility (LAMPF)‘“’ provide a means to produce larger quantities of 52Fe. * Bio-Rad Ag 1 x 8.
These machines produce 52Fe by 55Mn@, 4n), or by spallation reactions on targets with 2 > 26. SAHA and FARRER(‘*)studied the (p,4n) reaction using 65 MeV protons on a manganese dioxide target irradiated at OS@ Typically, the irradiation lasted for 1 h and produced 80&i of activity, a yield of 160 @i/pAh. The “Fe was separated by dissolving the MnO, in HCl and eluting through an anion exchange column, stripping the column and repeating the resin step. The separation took 2 h and the chemical yield was 70--80%. They estimate 55Fe production at less than 3% of 52Fe (EOB). The linacs at LAMPF and BLIP produce protons for other uses, but have been equipped with isotope production facilities. These accelerators produce protons of 800 and 200MeV at currents of 300 and 70 PA, respectively. BLIP routinely produces 52Fe for medical use by irradiating a 2.5 g/cm2 manganese powder target. The proton.energy is degraded in the target from 70 MeV to 50 MeV. An irradiation at 70 fi for 15 h will produce 115 mCi of $*Fe (EOB). “Fe is less than 0.7% ‘*Fe levels at EOB. This contamination level is low enough to allow administration to patients. The final, production method is by spallation. A target of 2 higher than iron is irradiated in a beam higher than lOOMeV, typically. The incident proton knocks out a number of protons and neutrons. SODD et al.” 3, used targets of manganese cobalt, nickel and copper to measure ‘*Fe production from hydrochloric acid into ether. The cross section for the reaction with nickel is 1.35 mb, about a factor of 10 higher than for cobalt or copper. The targets were irradiated with an external beam and of 50nA and monitored by 24Na production in aluminum. “Fe yield is 3.3% (EOB) and 59Fe yield is 0.16%. Radiation dosage from 59Fe is high since it decays by &emission and emits several high energy y-rays and has a 45 day half-life. A trial spallation production run was done at BLIP.(r4i A 20mm nickel foil was irradiated by
17
Technical Note TABLE 1.
Reaction
Particle 3He
“He P
52Fe production reactions
Particle energy
52Cr(3He, 311) 52Cr(3He, 3n) 52Cr(3He, 3n) “°Cr(4He, 2n) 50Cr(4He, 2n) 5sMn(p, 4n) “Mn(p, 4n) Nib. spallation) Ni(p, spallation) Nib. spallation)
45.5 33 40 65 30 65 70 200 588 800
Thick target yield (KilpAh)
Reference
50 20 50 8 3.3 160 -110 61* 700t 3300t
(8) (1) (9) (6) (7) (12) (16) (16) (13) (14)
* Thin target yield. t Estimated from cross-section measurement.
200 MeV protons, degrading the beam about 1.5 MeV. A 15 h irradiation at 70 PA produced 70 mCi at EOB. The relative production of 55Fe and 59Fe was 2.0 and 0.15% respectively. Obviously, a thicker target would increase yield significantly. The foil was relatively impure and introduced a high stable iron content to the final product, which would inhibit the use of the 52Fe in a compact generator system. At LAMPF, the cross section for spallation on a nickel target was measured at 800 MeV at an integrated current of 1 PA. They report a value of 1.54 mb for “Fe and 0.306mb for 59Fe. The chemical yield for the separation is 96%.‘15) They project an 52Fe yield of 8.3 Ci at half-saturation, assuming a target thickness of 2.3 cm and a 300 pA current. Recently a stack of foils was irradiated and processed producing 1 Ci EOB after a 16 h irradiation!‘@ The intensity of the beam passing through,the target was not known, because the beam spot was larger than the 1 in. diameter targets. The target was processed, 52Fe isolated and delivered to the West Coast in 24 h.
3. Discussion The production of 52Fe for medical use’has, until this time, been done for injection into patients. The development of the generatorc4i has increased potential uses for the radionuclide. Simultaneously, the requirements for radionuclidic purity have changed as well as the quantities needed. The specific activity of the 52Fe is also a factor since the generator size is dictated by the amount of iron present. The current generator utilizes an anion exchange resin,* 10&200 mesh, in a column 2 mm (i.d.) by 40 mm. The resin is supported at the top and bottom by glass wool plugs. 52mMn is eluted in 8 N HCl at a yield of 75%. Breakthrough is one part in 10,ooO or less. The elution is complete in two column volumes, 0.25 ml. While the normality of the HCl is high, evap* Bio-Rad Ag 1 x 8. t Cyclotron Corporation.
oration and dissolution in an appropriate buffer can be done in a few minutes. Mn(II) has shown itself to be a promising myocardial imaging agent. “‘I Its rapid blood clearance and high myocardial concentration both indicate a shortlived manganese radionuclide would be ideally suited for this use. The short processing time is necessary to prevent decay losses. The production capabilities of the reactions are summarized in Table 1. The spallation reaction has the highest yield, obviously, and provides the best source of 52Fe for use in a generator system. The high level of 55Fe and 59Fe would be problematic if the 52Fe were to be injected directly, but not in a generator. A 100mCi generator would yield 2OOnCi of “Fe and 15 nCi of 59Fe or less per elution. The large targets required by these higher energy machines require longer workup times and greater volumes of reagents. It is imperative that these be extremely pure in order to hold levels of carrier iron to a minimum. Since the high current machines are capable of production by spallation, it would be unnecessary to produce 52Fe by bombarding manganese. For cyclotrons able to produce 70 MeV proton beams, the current is generally so low that production is better done using a 3He beam. Even relatively low energy machines could be used to produce 52Fe. A CS-15,t commonly found around the country, has an internal current of 3001_1Afor 3He. Even at its energy of 24 MeV, it is still able to produce 1.5 mCi/h, or 12 mCi in 8 h, enough for a generator of useful size. Even a 4He beam could be used since the high levels of 55Fe produced by 52Cr(4He,n), would be easily tolerated in a generator system. The threshold for the reaction, 15 MeV, would eliminate using a CS-15 which produces 4He at this energy. but would not preclude using other cyclotrons with a slightly higher energy. Production at low energy increases the “Fe contamination since the energy is nearer to the peak in the excitation function for the (‘He, n) reaction In summary, many production methods for s2Fe provide many sources of supply for the s2Fe-52mMn
Technical Note
18
LEDERERC. M. and SHIRLEYV. S. Table of ISOCopes,7th edn, p. 146. Wiley, New York (1978). YANOY. and ANGER H. 0. Int. J. uppl. Radiat.
generator. Production could be tailored to the needs of the generator user; multicurie generators could be produced for hospitals performing many procedures or small generators could be produced on a day to day basis using relatively small cyclotrons nearby.
Isotopes 16, I53 (1965).
THAKURM. L., NUNN A. D. and WATERSS. I,. Int. J. appl. Radiat. lsotopes 22, 481 (1971).
Acknowledgements-The
authors would like to thank Karen Knoerr for manuscript preparation. Research support is provided by the Office of Health and Environmental Research, U.S. Department of Energy. One of the authors (R.W.A.) would like to thank the Argonne Center for Educational Affairs for support during the course of this work.
References
8. GREENEM. W., LEBOWIT~E., RICHARDSP. et al. Int. J. appl. Radiat. Isotopes 21, 719 (1970).
9.
MURAKAMIY., AKIKA F. and EZAWA 0. Radiopharmaceuticals and Lahelled Compounds, p. 257.
IAEA, Vienna (1973). 10. SERAFINIA. N. and BEAVERJ. E. Medical Cyclotrons in Nuclear Medicine, p. 16. Karger, Base1 (1978). Il. Ibid., p. 34. 12. SAHA G. B. and FARRER P. A. Int. J. appl. Radiat. Isotopes 22, 495 (1971).
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