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An improved technetium-99m generator for medical applications
332
Technical notes
decontamination rather than its inertness. There were five valves on the manifold connected to the reaction flask (75 ml capacity 1800 lb/in2 rating), a connection to vacuum, a cylinder of SF** a vacuum gauge, and a one-liter gas measuring cylinder. The 75 ml reaction vessel was charged 695 mg (5 mM) bromoacetic-l-Cl4 acid and then connected to the system using a minimum amount of thread compound. The bottom of the reactor was frozen in liquid N2 and the air evacuated from the entire manifold. SF, (16 mM 60% excess) was metered out into the measuring tank using the vacuum gauge to give an accuracy of i-5%. The SF, was then transferred to the frozen bromoacetic-l-Cl4 acid and the reactor closed off. The tank was allowed to come to room temperature, immersed in a wax bath, and then slowly over the course of 1 hr raised to 15O”C, at which temperature it was held for 4 hr. The cylinder of SF, was then removed from the manifold. In its place was attached a 75 ml stainlesssteel valved tank containing a small Teflon-coated stirring bar and 6 g KOH dissolved in 10 ml H,O. By theory, 4.5 g (80 mM) KOH would be required to neutralize all the acidic components of the reaction mixture. The cylinder was frozen in liquid nitrogen the contents of the reactor distilled into it, and the whole mixture allowed to warm to room temperature with stirring. When the mixture had been stirred for i hr after reaching room temperature, the cylinder with the valve attached was removed from the system and an adapter for rubber tubing attached to the valve. The tank was then connected to a glass vacuum system in series with a drying tube of Ascarite and one of P,O, suspended on glass beads. The product was pulled through these reagents and transferred to a tared stopcock bulb on the vacuum line. The crude yield amounted to 532 mg (3.26 mM), or 65% by theory. Analysis by gas chromatography on a Carbowax 20 M column indicated greater than 95% purity. The crude C14F,CH2Br was pure enough to be carried on to the next step. If pure material is required for other purposes, preparative gas chromatography may be carried out on a 4 in. x 8 ft. 20% silicone oil 200 on Diatoport column at 65°C. I-C14-l,l,l-tr$oroethanol In a Pyrex tube 12 mm in diameter was placed 335 mg (3.42 mM) of potassium acetate, 0.20 ml H,O and 1 ml freshly distilled diethylene glycol. The tube was restricted for sealing off 4 in. from the bottom. After attaching to the vacuum line, the tube * Obtained from Organic Chemicals Department, E. I. Du Pont & Co., Wilmington, Delaware.
was frozen in liquid N,, evacuated, and the crude C14F,CHsBr transferred therein. The tube was sealed off and placed in a high-pressure cylinder. After applying 500 lb/in2external pressureof nitrogen, shaking was commenced, the temperature was raised over 4 hr to 170°C and the cylinder left at this temperature for an additional 12 hr. The cylinder was cooled, the pressure vented and the tube removed. After cooling in ice and cracking open, the tube was attached to the vacuum line via a CaSO, drying tube. The CY4FsCH20H was distilled into a tared stopcock bulb and found to weigh 260 mg (2.6 mM) for a yield of 80%. Gas chromatographic analysis on a 12 ft. x t in. silicone gum rubber column indicated better than 98% purity. R. L. EHRENPELD Halocarbon Laboratories, Inc. Hackenrack, N. J. J. L. MORGENTHAU,JR. New England Nuclear Corp. Boston, Mass. References MORGENTHAU J. L., JR. Unpublished work. SHUKYSJ. G. U.S. Patent No. 2,830,007 (1948). SWARTS F. C.R. Acad. Sci. Paris 197, 1261 (1933). STEWARD R. and LINDEEN R. VAN DER Disc. Faraday Sot. No. 29, 2 11 ( 1960). 5. HASEKW. R., SMITHW. C. and ENGELHARTV. A. J. Amer. them. Sot. 82, 543 (1960).
1. 2. 3. 4.
International Journal of Applied Radiation and Isotopes, 1965, Vol. 16, pp. 332-334. Pergarnon Press Ltd. Printed in Northern Ireland An
Improved Technetium-99m Generator for Medical Applications * (Received 30 November 1964) Introduction
A Tcsem generator which uses fission product Moe9 as molybdate sorbed on alumina has been available for some time.tl-4) However, difficulties have been encountered because of radioactive impurities, such as Rulss and Ilss, found in fission product MOBS and because of a slight solubility of alumina in the 0.1 M For an acceptable product, an HNO, eluant. * Research sponsored by the U. S. Atomic Energy Commission under contract with the Union Carbide Corporation.
Technicalnotes
333
4.00 Tim. lu .oo 2.00 4.00 I?~ 1o:OO 12.00
0.50
:z% 1s:Oa 20.00 22.00 %Z 28.00 30.00 32.00 34.00
0.20
:E ‘4;:;;
E z
‘YE 4l3:oo 50.00
0.10
5
:tz ::% 60.00 62.00 64.00 66.00 68.00
0.05
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0.02
sl?:oo
1111111111111111
O.Ol_ 0
10
20
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I I III 40
l Ill
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111111ill all
60
50
70
80
llIII1 90
Et88 94.00 96.00 98.00 100.00
O.-l?6 0.311 0.415 0.495 0.554 0.598 0.630 0.652 EC 01678 0.678 0.675 0.670 0.663 0.655 0.646 0.636 0.626 0.615 0.604 0.593 0.582 0.571 0.560 0.549 0.538 0.528 0.517 0.5w 0.497 0.487 0.477 0.467 0.458 0.448 0.439 0.430 0.421 0.413 0.404 z% o:sso 0.372 0.365 0.357 0.350 0.343 0.336
400
hr
FIN. 1 additional purification step involving solvent extraction with methyl ethyl ketone is used to separate Tcnsm from these impurities. The product is specified to have >99.99 percent radiochemical purityt4) and GREENE@) has indicated < 10m3percent radiocontamination. Technetium-99m is of particular interest in medical and biological scanning studies(s*7) because of its short half-life (6.0 hr) and simple decay scheme (a single 0.143 meV photon). The radiation may be readily collimated, thereby allowing better localization and providing better differentiation. Because of these considerations, the whole-body dose is kept at a minimum. The short-lived Tcgsn, may be obtained from the longer-lived (67 hr) Moss parent by fixing the parent on an ion-exchange medium from which the daughter activity may be repeatedly milked. After a milking, the regenerated Tcggm-
activity reaches
a maximum again in 23 hr. The growth and decay curves for Tcnen and MoDg are given in Fig. 1. The oarent. MonO. decavs to ~~~~~ (86%) and to TcDs’(14~0jts).* ’ Description
of generator
The generator reported here is a modification of the one described above. The generator is prepared by loading a 0.5 in. i.d. Pyrex ion-exchange column, fitted with a coarse fritted glass disc, to a depth of 3-I in. with activated Alcoa alumina, grade F-20. The alumina is conditioned by rinsing with about 50 ml of 0.01 M HCl. An ammoniacal solution of reactor-produced Moss, with specific activity > 1 c/g, * A recent work by CROWTHER and E~~arno~t~) indicates 87.6 percent for the value of the decay of the Moss parent to tbe 6.0-hr isomeric level of TP.
334
Technical notes
is evaporated to drive off the ammonia. The residue of ammonium molybdate is taken up in 10-20 ml of 0.01 M HCl and passed through the column. This procedure fixes >99 percent of the Moss-activity on the alumina. In order to prepare the system for milking, the column is washed with 30 ml of methyl ethyl ketone and allowed to drain, then, after a few minutes, the TcgDm-activity is eluted with 20 ml of methyl ethyl ketone containing 5 vol. y. 0.01 M HCl. These solutions are discarded. After allowing time for sufficient Tcssm to grow into the system (Fig. I), the generator is milked by passing 20 ml of the eluant through the column. This is sufficient to remove >75 percent of the Tcssm-activity and requires about 5 min to complete. The eluant solution is evaporated to dryness, and the Tcssm-activity taken up in an appropriate solvent, e.g. physiological-salt solution. No alumina or other solids has ever been detected in the Tcssm upon evaporation. Results In the generators tested, the radiochemical purity of the TcQQm improved steadily with each successive milking and gave a product of higher purity than that from currently available generators. For example, a generator containing 230 mc of Moss (170 mg total MO) had 3 x lOA percent Moss activity in the first milking; this decreased to 1 x 10”’ percent in the second milking and then to <5 x 1O-5 Although percent Moss in all later milkings. reactor-produced MO Q0 does contain a small amount of Nbsz and possibly a trace of Zr*O-activity, neither these nor any other radiocontaminants were detected in any Tcsgm milkings. The search for radiocontaminants was made by allowing the Tcssm to decay through lo-20 half-lives and counting the sample for lOO-min periods with a 3 x 3 in. NaI(T1) crystal with a 512-channel analyzer. Three separate generators continued to operate satisfactorily for over 30 milkings. Such a generator has been used at the Oak Ridge Institute of Nuclear Studies. The effects of several variables in the operation of the generator have been determined: 1. The elution rate of Tcggm increases with increasing water content of methyl ethyl ketone, with >2.5 vol. o/0 He0 required to effect a satisfactory elution. 2. An increase in HCl content of the aqueous solution added to the methyl ethyl ketone slightly inhibits the elution of Tcsgm but greatly decreases the amount of Mogs eluted, thereby playing an important role in improved product purity. 3. The quantity of molybdenum loaded on the column in a single charge has no detectable
effect up to 200 mg of molybedenum. This is sufficient to charge a generator with up to 300 mc of MoQO. It might also be noted that a generator originally charged with 170 mg of molybdenum was successfully recharged with a second 170-mg sample with >99 percent of the activity adsorbed each time. Acknowledgments-The author is pleased to express his appreciation to A. P. CALLAHAN for his assistance and to Dr. J. J. PINAJIAN for his invaluable aid and counsel. J. F. ALLEN Oak Ridge National Laboratory Oak Ridge, Tennessee* * Present address: Geology, Clemson Carolina.
Department University,
of Chemistry and Clemson, South
References National Laboratory Catalog, Proc1. Brookhaven essed Isotopes, New York (1960). 2. STANG L. G., JR. and RICHARDS P. Nucleonics 22, (1) 46 (1964). 3. GREENE M. W., DOERING R. F. and HILLMAN M. Isotojes Rad. Technol. 1,(2) 152 (1963-1964). 4. TUCKER W. D., GREENE M. W. and MURRENHOFF A. P. Atompraxis 5, 163 (1962). Report 5. WEISS A. and HILLMAN M. USAEC BNL-799, p. 67, Brookhaven National Laboratory (1963). HARPER P. V., BECK R., CHARLESTON D. and LATHROP K. A. Nucleonics 22, (1) 50 (1964). LATHROP K. A. and HARPER P. V. USAEC Report TID-7689, p. 5 (1964). [Abstract.] DZHELEPOV B. S. and PEKER L. K. Decay Schemes of Radioactive Nuclei, p. 256, Pergamon Press (1961). CROWTHER P. and ELDRIDGE J. S. To be published.
InternationalJournal ofApplied Radiation and Isotopes, 1965, Vol. 16, pp. 334-336.
Pergamon Press Ltd. Printed in Northern Ireland
On the Stability of some Liquid Scintillator Solutions (Received 9 November 1964) IN A recent article by ERDTMANN~), it was emphasized once again that cations, if brought into a scintillator liquid, do not always form stable solutions if no special precautions are taken. In addition to his work the results of our experiments on the same subject may be presented here.
Technical notes
decontamination rather than its inertness. There were five valves on the manifold connected to the reaction flask (75 ml capacity 1800 lb/in2 rating), a connection to vacuum, a cylinder of SF** a vacuum gauge, and a one-liter gas measuring cylinder. The 75 ml reaction vessel was charged 695 mg (5 mM) bromoacetic-l-Cl4 acid and then connected to the system using a minimum amount of thread compound. The bottom of the reactor was frozen in liquid N2 and the air evacuated from the entire manifold. SF, (16 mM 60% excess) was metered out into the measuring tank using the vacuum gauge to give an accuracy of i-5%. The SF, was then transferred to the frozen bromoacetic-l-Cl4 acid and the reactor closed off. The tank was allowed to come to room temperature, immersed in a wax bath, and then slowly over the course of 1 hr raised to 15O”C, at which temperature it was held for 4 hr. The cylinder of SF, was then removed from the manifold. In its place was attached a 75 ml stainlesssteel valved tank containing a small Teflon-coated stirring bar and 6 g KOH dissolved in 10 ml H,O. By theory, 4.5 g (80 mM) KOH would be required to neutralize all the acidic components of the reaction mixture. The cylinder was frozen in liquid nitrogen the contents of the reactor distilled into it, and the whole mixture allowed to warm to room temperature with stirring. When the mixture had been stirred for i hr after reaching room temperature, the cylinder with the valve attached was removed from the system and an adapter for rubber tubing attached to the valve. The tank was then connected to a glass vacuum system in series with a drying tube of Ascarite and one of P,O, suspended on glass beads. The product was pulled through these reagents and transferred to a tared stopcock bulb on the vacuum line. The crude yield amounted to 532 mg (3.26 mM), or 65% by theory. Analysis by gas chromatography on a Carbowax 20 M column indicated greater than 95% purity. The crude C14F,CH2Br was pure enough to be carried on to the next step. If pure material is required for other purposes, preparative gas chromatography may be carried out on a 4 in. x 8 ft. 20% silicone oil 200 on Diatoport column at 65°C. I-C14-l,l,l-tr$oroethanol In a Pyrex tube 12 mm in diameter was placed 335 mg (3.42 mM) of potassium acetate, 0.20 ml H,O and 1 ml freshly distilled diethylene glycol. The tube was restricted for sealing off 4 in. from the bottom. After attaching to the vacuum line, the tube * Obtained from Organic Chemicals Department, E. I. Du Pont & Co., Wilmington, Delaware.
was frozen in liquid N,, evacuated, and the crude C14F,CHsBr transferred therein. The tube was sealed off and placed in a high-pressure cylinder. After applying 500 lb/in2external pressureof nitrogen, shaking was commenced, the temperature was raised over 4 hr to 170°C and the cylinder left at this temperature for an additional 12 hr. The cylinder was cooled, the pressure vented and the tube removed. After cooling in ice and cracking open, the tube was attached to the vacuum line via a CaSO, drying tube. The CY4FsCH20H was distilled into a tared stopcock bulb and found to weigh 260 mg (2.6 mM) for a yield of 80%. Gas chromatographic analysis on a 12 ft. x t in. silicone gum rubber column indicated better than 98% purity. R. L. EHRENPELD Halocarbon Laboratories, Inc. Hackenrack, N. J. J. L. MORGENTHAU,JR. New England Nuclear Corp. Boston, Mass. References MORGENTHAU J. L., JR. Unpublished work. SHUKYSJ. G. U.S. Patent No. 2,830,007 (1948). SWARTS F. C.R. Acad. Sci. Paris 197, 1261 (1933). STEWARD R. and LINDEEN R. VAN DER Disc. Faraday Sot. No. 29, 2 11 ( 1960). 5. HASEKW. R., SMITHW. C. and ENGELHARTV. A. J. Amer. them. Sot. 82, 543 (1960).
1. 2. 3. 4.
International Journal of Applied Radiation and Isotopes, 1965, Vol. 16, pp. 332-334. Pergarnon Press Ltd. Printed in Northern Ireland An
Improved Technetium-99m Generator for Medical Applications * (Received 30 November 1964) Introduction
A Tcsem generator which uses fission product Moe9 as molybdate sorbed on alumina has been available for some time.tl-4) However, difficulties have been encountered because of radioactive impurities, such as Rulss and Ilss, found in fission product MOBS and because of a slight solubility of alumina in the 0.1 M For an acceptable product, an HNO, eluant. * Research sponsored by the U. S. Atomic Energy Commission under contract with the Union Carbide Corporation.
Technicalnotes
333
4.00 Tim. lu .oo 2.00 4.00 I?~ 1o:OO 12.00
0.50
:z% 1s:Oa 20.00 22.00 %Z 28.00 30.00 32.00 34.00
0.20
:E ‘4;:;;
E z
‘YE 4l3:oo 50.00
0.10
5
:tz ::% 60.00 62.00 64.00 66.00 68.00
0.05
:Kz ;;:g 7l3:oo :Ez I??;:
0.02
sl?:oo
1111111111111111
O.Ol_ 0
10
20
I III 30
I I III 40
l Ill
TIME.
111111ill all
60
50
70
80
llIII1 90
Et88 94.00 96.00 98.00 100.00
O.-l?6 0.311 0.415 0.495 0.554 0.598 0.630 0.652 EC 01678 0.678 0.675 0.670 0.663 0.655 0.646 0.636 0.626 0.615 0.604 0.593 0.582 0.571 0.560 0.549 0.538 0.528 0.517 0.5w 0.497 0.487 0.477 0.467 0.458 0.448 0.439 0.430 0.421 0.413 0.404 z% o:sso 0.372 0.365 0.357 0.350 0.343 0.336
400
hr
FIN. 1 additional purification step involving solvent extraction with methyl ethyl ketone is used to separate Tcnsm from these impurities. The product is specified to have >99.99 percent radiochemical purityt4) and GREENE@) has indicated < 10m3percent radiocontamination. Technetium-99m is of particular interest in medical and biological scanning studies(s*7) because of its short half-life (6.0 hr) and simple decay scheme (a single 0.143 meV photon). The radiation may be readily collimated, thereby allowing better localization and providing better differentiation. Because of these considerations, the whole-body dose is kept at a minimum. The short-lived Tcgsn, may be obtained from the longer-lived (67 hr) Moss parent by fixing the parent on an ion-exchange medium from which the daughter activity may be repeatedly milked. After a milking, the regenerated Tcggm-
activity reaches
a maximum again in 23 hr. The growth and decay curves for Tcnen and MoDg are given in Fig. 1. The oarent. MonO. decavs to ~~~~~ (86%) and to TcDs’(14~0jts).* ’ Description
of generator
The generator reported here is a modification of the one described above. The generator is prepared by loading a 0.5 in. i.d. Pyrex ion-exchange column, fitted with a coarse fritted glass disc, to a depth of 3-I in. with activated Alcoa alumina, grade F-20. The alumina is conditioned by rinsing with about 50 ml of 0.01 M HCl. An ammoniacal solution of reactor-produced Moss, with specific activity > 1 c/g, * A recent work by CROWTHER and E~~arno~t~) indicates 87.6 percent for the value of the decay of the Moss parent to tbe 6.0-hr isomeric level of TP.
334
Technical notes
is evaporated to drive off the ammonia. The residue of ammonium molybdate is taken up in 10-20 ml of 0.01 M HCl and passed through the column. This procedure fixes >99 percent of the Moss-activity on the alumina. In order to prepare the system for milking, the column is washed with 30 ml of methyl ethyl ketone and allowed to drain, then, after a few minutes, the TcgDm-activity is eluted with 20 ml of methyl ethyl ketone containing 5 vol. y. 0.01 M HCl. These solutions are discarded. After allowing time for sufficient Tcssm to grow into the system (Fig. I), the generator is milked by passing 20 ml of the eluant through the column. This is sufficient to remove >75 percent of the Tcssm-activity and requires about 5 min to complete. The eluant solution is evaporated to dryness, and the Tcssm-activity taken up in an appropriate solvent, e.g. physiological-salt solution. No alumina or other solids has ever been detected in the Tcssm upon evaporation. Results In the generators tested, the radiochemical purity of the TcQQm improved steadily with each successive milking and gave a product of higher purity than that from currently available generators. For example, a generator containing 230 mc of Moss (170 mg total MO) had 3 x lOA percent Moss activity in the first milking; this decreased to 1 x 10”’ percent in the second milking and then to <5 x 1O-5 Although percent Moss in all later milkings. reactor-produced MO Q0 does contain a small amount of Nbsz and possibly a trace of Zr*O-activity, neither these nor any other radiocontaminants were detected in any Tcsgm milkings. The search for radiocontaminants was made by allowing the Tcssm to decay through lo-20 half-lives and counting the sample for lOO-min periods with a 3 x 3 in. NaI(T1) crystal with a 512-channel analyzer. Three separate generators continued to operate satisfactorily for over 30 milkings. Such a generator has been used at the Oak Ridge Institute of Nuclear Studies. The effects of several variables in the operation of the generator have been determined: 1. The elution rate of Tcggm increases with increasing water content of methyl ethyl ketone, with >2.5 vol. o/0 He0 required to effect a satisfactory elution. 2. An increase in HCl content of the aqueous solution added to the methyl ethyl ketone slightly inhibits the elution of Tcsgm but greatly decreases the amount of Mogs eluted, thereby playing an important role in improved product purity. 3. The quantity of molybdenum loaded on the column in a single charge has no detectable
effect up to 200 mg of molybedenum. This is sufficient to charge a generator with up to 300 mc of MoQO. It might also be noted that a generator originally charged with 170 mg of molybdenum was successfully recharged with a second 170-mg sample with >99 percent of the activity adsorbed each time. Acknowledgments-The author is pleased to express his appreciation to A. P. CALLAHAN for his assistance and to Dr. J. J. PINAJIAN for his invaluable aid and counsel. J. F. ALLEN Oak Ridge National Laboratory Oak Ridge, Tennessee* * Present address: Geology, Clemson Carolina.
Department University,
of Chemistry and Clemson, South
References National Laboratory Catalog, Proc1. Brookhaven essed Isotopes, New York (1960). 2. STANG L. G., JR. and RICHARDS P. Nucleonics 22, (1) 46 (1964). 3. GREENE M. W., DOERING R. F. and HILLMAN M. Isotojes Rad. Technol. 1,(2) 152 (1963-1964). 4. TUCKER W. D., GREENE M. W. and MURRENHOFF A. P. Atompraxis 5, 163 (1962). Report 5. WEISS A. and HILLMAN M. USAEC BNL-799, p. 67, Brookhaven National Laboratory (1963). HARPER P. V., BECK R., CHARLESTON D. and LATHROP K. A. Nucleonics 22, (1) 50 (1964). LATHROP K. A. and HARPER P. V. USAEC Report TID-7689, p. 5 (1964). [Abstract.] DZHELEPOV B. S. and PEKER L. K. Decay Schemes of Radioactive Nuclei, p. 256, Pergamon Press (1961). CROWTHER P. and ELDRIDGE J. S. To be published.
InternationalJournal ofApplied Radiation and Isotopes, 1965, Vol. 16, pp. 334-336.
Pergamon Press Ltd. Printed in Northern Ireland
On the Stability of some Liquid Scintillator Solutions (Received 9 November 1964) IN A recent article by ERDTMANN~), it was emphasized once again that cations, if brought into a scintillator liquid, do not always form stable solutions if no special precautions are taken. In addition to his work the results of our experiments on the same subject may be presented here.