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Rapid separation of generator-produced gallium-68 from EDTA Eluate
Technical notes
44
to remain indefinitely, giving a radiation dose of about 200 mrad./mCi. 3-hr urine collections from two patients showed excretion of less than 1 per cent of the dose in this time. This retention of activity by the liver, combined with the extremely low blood activity, is sufficient to give a reasonable liver scan by 4 hr post-injection, when the 1iver:lung activity has reached about 2 : 1. Thus the material is suitable for both lung scanning and subsequent liver scanning. It is stable and sterile, and patient hazards due to toxicity and radiation exposure are within currently accepted limits. GAVIN D. NEILL The Regional Physics Department 7 Dudhope Terrace Dundee DO3 6HG Scotland
References CRAICINM. D., WEBBER M. M., VICTERY W. K. and PINTAUROD. J. nucl. Med. lo,62 1 (1969). M&FEE J. G., STERN H. S., FUEGER G. F. et al. J. nucl. Med. 5, 936 (1964).
A major advantage of ssGa is its availability from a long-lived parent (6*Ge, TIi2 = 280 days). Daughter 68Ga is readily separated from 6sGe adsorbed on an alumina support by elution with 0.005 M sodium ethylenediaminetetraacetate (EDTA) adjusted to pH 7.t’) However, for use as an effective agent for scanning tumor tissue or visualizing the reticuloendothelial system, s*Ga should be separated from the EDTA present in the eluate. Although this can be done efficiently by solvent extraction techniques, a less time-consuming method is desirable. We report here a rapid as well as efficient ion exchange method for this separation. The 6sGa-EDTA chelate is dissociated by addition of concentrated HCl;ts) under such conditions EDTA passes through an anion resin column (2-cm high by 1.5 cm in dia.) while the s*Ga is bound to the resin as the chloride complex. The ssGa can then be eluted with either distilled water or dilute HCl. Figure 1 shows the apparatus (composed of two separate pieces) used in the separation procedure. This particular design was adopted to facilitate rapid and reproducible separations of 6sGa for human use.
TAPLAN G. V., DORE E. K., JOHNSOND. E. and KAPLAN H. S. J. nucl. Med. 5,259 (1964). PA~ON D. D., GARCIA E. N., WEBBER M. M., Am. J. Roentgen. 97, 880 (1966).
International JoumalofApplied Radiation and Isotopes, 197 I, Vol. 22, pp. 44-45. Pergamon Press. Printed in Northern Ireland
Rapid Separation of Generator-Produced Gallium-68 from EDTA Eluate (Received 16 April 1970;
in revisedform 23 Jub
1970)
GALLIUM-68, a short half-life positron emitter, has been used as an agent for visualization of both brain and bone lesions.t1*2) Recently EDWARDS and HAYES’~*~) and HAYES et akc5) have reported use of 67Ga (TI,z = 78 hr) for the detection of nonosseous tumors. Despite its short half-life 6sGa (T,,, = 68 min) may also be useful as a tumor-scanning agent, if adequate means can be found for promoting the rapid clearance of gallium from nontumor tissues. The positron decay mode of 6sGa would provide for tomographic scanning by coincidencedetection techniques. Gallium-68 is also an effective label for hydrous ferric oxide colloid preparations for liver and bone-marrow scanning, particularly when this colloid is prepared by heat hydrolysis.(6)
LTER CLOTH AND ETAINING RING
EDTA 6 N HCI
FIG. 1. Artist’s drawing of apparatus used for generator separation of ssGa from EDTA eluate (not to scale; see text for pertinent dimensions).
Technical notes The lower portion is a glass column, 1.5 cm in inside diameter and approximately lo-cm long, fitted with a variable-flow Teflon stopcock. The .. upper addltlon unit fits over the lower column and also has an adjustable stopcock. The addition unit is positioned so that the inside tube is just above the top of the resin bed to prevent splashing of the sides of the column during additions. The outer tube keeps the smaller inside tube from touching the sides of the addition unit when it is withdrawn from the lower unit. Bio-Rad AG 1 anion-exchange resins (Bio-Rad Laboratories, Richmond, California) with various degrees of cross linkage were used in developmental studies; all were 50-100 mesh and in the chloride form. Bio-Rad AG l-X2 (2 per cent cross linkage) was ultimately chosen as best suited to this rapidseparation procedure. Before use the AG l-X2 resin is washed thoroughly with distilled water and 6 N HCl. A 2-cm exchange column is then prepared over a glass wool plug in the lower unit. A piece of filter cloth and a perforated Teflon disc and Teflon retaining ring are used to hold the bed in place. Just before use of the column the bed is conditioned with repeated washes of 6 N HCI; between uses the bed is stored under 0.1 N HCl. The eluate (20 ml) from the ssGa generator(‘) is added to an equal volume of concentrated HCI. This mixture is then transferred to the reservoir of the addition unit and allowed to pass through the ion-exchange column at a rate of approximately 15 ml/mitt, the flows through the two stopcocks having been adjusted ahead of time to maintain a minimum height of solution above the filter cloth during passage of the mixture. The addition unit is replaced by a clean one and the column is then washed repeatedly with 6 N HCl, progressively larger volumes being used to assure thorough rinsing of the column wall above the retaining ring. After this washing, a volume of O-1 N HCl roughly equal to the bed volume (-3 ml for the 2 x 1*5-cm bed) is passed through the column and discarded. The 6sGa is then eluted in the next 5 ml of eluate. The eluate is approximately 2 N with respect to HCl; further processing will depend on the final 6sGa product desired. Recovery of @Ga from the Bio-Rad AG 1-X2 resin column was 98-99 per cent. AG 1-X4 and AG l-X8 resins gave slightly lower recoveries while that from the AG l-X10 was only 85 per cent. The HCI concentration of the eluant has no effect on the @Ga elution between 0-l N and 1.0 N. However, with appreciably higher acid concentrations, the recovery of the 6*Ga falls drastically. The height of
45
the column (between 2 and 8 cm) also has little effect on the ssGa recovery, but below 2 cm the column cannot retain the entire amount of 6*Ga added at the rapid rate used, and approximately 5-10 per cent of the activity passes through with the EDTA. The final eluate containing the ssGa has been tested for contamination by EDTA and aluminum (arising from the alumina support in the generator) with the calorimetric methods described by BRADY and GWILT(~)and SANDELL.~~)Total contamination by EDTA for any one separation run was less than 0.5 pg and that for A1+3 approximately 3 pg. Tests using USP techniques indicate that this separation technique introduces no pyrogens in the final product. The separation procedure requires approximately 15 min. Sterility tests would have to be made on the product from any further processing of the separated 8sGa. J. E. CARLTON R. L. HAYES Medical Division Oak Ridge Associated Universities* Oak Ridge, Term. 37830, U.S.A.
* Under contract with the United States Atomic Energy Commission. References A. 1. SCHAER L. R., ANGERH. 0. and GOTTSCHALK J. Am. med. Ass. 198,811 (1966). R. M., AN~REWSG. A., EDWARDSC. L. 2. KNISELEY and HAYESR. L. Radial c&n. N. Am. 7,265 (1969). 3. EDWARDSC. L. and HAYES R. L. J. nucl. Med. 10, 103 (1969). 4. EDWARIISC. L. and HAYESR. L. J. Am. med. Ass. 212, 1182 (1970). B., SWARTZENDRUBER D. C., 5. H&ES R. L., NELSON CA~LTONJ. E. and BYRD B. L. Science 167,289 (1970). HAYES R. L., CARLTONJ. E., BYRD B. L. and RAFTERJ. J. nucl. Med. 8, 302 (1967). GREENEM. W. and TUCKERW. D. ht. J. appl. Radiat. Isotopes 12, 62 (1961). SAITOK. and TSIJCHIMOTO M. J. inorg. nucl. Chem. 23, 71 (1961). BRADYG. W. F. and GWILTJ. R. J. a&l. Chem. 12, 79 (1962). 10. SANDELLE. B. Colorimetriz Determination of Traces of Metals, Vol. 3, p. 116. Inter-science, New York.
44
to remain indefinitely, giving a radiation dose of about 200 mrad./mCi. 3-hr urine collections from two patients showed excretion of less than 1 per cent of the dose in this time. This retention of activity by the liver, combined with the extremely low blood activity, is sufficient to give a reasonable liver scan by 4 hr post-injection, when the 1iver:lung activity has reached about 2 : 1. Thus the material is suitable for both lung scanning and subsequent liver scanning. It is stable and sterile, and patient hazards due to toxicity and radiation exposure are within currently accepted limits. GAVIN D. NEILL The Regional Physics Department 7 Dudhope Terrace Dundee DO3 6HG Scotland
References CRAICINM. D., WEBBER M. M., VICTERY W. K. and PINTAUROD. J. nucl. Med. lo,62 1 (1969). M&FEE J. G., STERN H. S., FUEGER G. F. et al. J. nucl. Med. 5, 936 (1964).
A major advantage of ssGa is its availability from a long-lived parent (6*Ge, TIi2 = 280 days). Daughter 68Ga is readily separated from 6sGe adsorbed on an alumina support by elution with 0.005 M sodium ethylenediaminetetraacetate (EDTA) adjusted to pH 7.t’) However, for use as an effective agent for scanning tumor tissue or visualizing the reticuloendothelial system, s*Ga should be separated from the EDTA present in the eluate. Although this can be done efficiently by solvent extraction techniques, a less time-consuming method is desirable. We report here a rapid as well as efficient ion exchange method for this separation. The 6sGa-EDTA chelate is dissociated by addition of concentrated HCl;ts) under such conditions EDTA passes through an anion resin column (2-cm high by 1.5 cm in dia.) while the s*Ga is bound to the resin as the chloride complex. The ssGa can then be eluted with either distilled water or dilute HCl. Figure 1 shows the apparatus (composed of two separate pieces) used in the separation procedure. This particular design was adopted to facilitate rapid and reproducible separations of 6sGa for human use.
TAPLAN G. V., DORE E. K., JOHNSOND. E. and KAPLAN H. S. J. nucl. Med. 5,259 (1964). PA~ON D. D., GARCIA E. N., WEBBER M. M., Am. J. Roentgen. 97, 880 (1966).
International JoumalofApplied Radiation and Isotopes, 197 I, Vol. 22, pp. 44-45. Pergamon Press. Printed in Northern Ireland
Rapid Separation of Generator-Produced Gallium-68 from EDTA Eluate (Received 16 April 1970;
in revisedform 23 Jub
1970)
GALLIUM-68, a short half-life positron emitter, has been used as an agent for visualization of both brain and bone lesions.t1*2) Recently EDWARDS and HAYES’~*~) and HAYES et akc5) have reported use of 67Ga (TI,z = 78 hr) for the detection of nonosseous tumors. Despite its short half-life 6sGa (T,,, = 68 min) may also be useful as a tumor-scanning agent, if adequate means can be found for promoting the rapid clearance of gallium from nontumor tissues. The positron decay mode of 6sGa would provide for tomographic scanning by coincidencedetection techniques. Gallium-68 is also an effective label for hydrous ferric oxide colloid preparations for liver and bone-marrow scanning, particularly when this colloid is prepared by heat hydrolysis.(6)
LTER CLOTH AND ETAINING RING
EDTA 6 N HCI
FIG. 1. Artist’s drawing of apparatus used for generator separation of ssGa from EDTA eluate (not to scale; see text for pertinent dimensions).
Technical notes The lower portion is a glass column, 1.5 cm in inside diameter and approximately lo-cm long, fitted with a variable-flow Teflon stopcock. The .. upper addltlon unit fits over the lower column and also has an adjustable stopcock. The addition unit is positioned so that the inside tube is just above the top of the resin bed to prevent splashing of the sides of the column during additions. The outer tube keeps the smaller inside tube from touching the sides of the addition unit when it is withdrawn from the lower unit. Bio-Rad AG 1 anion-exchange resins (Bio-Rad Laboratories, Richmond, California) with various degrees of cross linkage were used in developmental studies; all were 50-100 mesh and in the chloride form. Bio-Rad AG l-X2 (2 per cent cross linkage) was ultimately chosen as best suited to this rapidseparation procedure. Before use the AG l-X2 resin is washed thoroughly with distilled water and 6 N HCl. A 2-cm exchange column is then prepared over a glass wool plug in the lower unit. A piece of filter cloth and a perforated Teflon disc and Teflon retaining ring are used to hold the bed in place. Just before use of the column the bed is conditioned with repeated washes of 6 N HCI; between uses the bed is stored under 0.1 N HCl. The eluate (20 ml) from the ssGa generator(‘) is added to an equal volume of concentrated HCI. This mixture is then transferred to the reservoir of the addition unit and allowed to pass through the ion-exchange column at a rate of approximately 15 ml/mitt, the flows through the two stopcocks having been adjusted ahead of time to maintain a minimum height of solution above the filter cloth during passage of the mixture. The addition unit is replaced by a clean one and the column is then washed repeatedly with 6 N HCl, progressively larger volumes being used to assure thorough rinsing of the column wall above the retaining ring. After this washing, a volume of O-1 N HCl roughly equal to the bed volume (-3 ml for the 2 x 1*5-cm bed) is passed through the column and discarded. The 6sGa is then eluted in the next 5 ml of eluate. The eluate is approximately 2 N with respect to HCl; further processing will depend on the final 6sGa product desired. Recovery of @Ga from the Bio-Rad AG 1-X2 resin column was 98-99 per cent. AG 1-X4 and AG l-X8 resins gave slightly lower recoveries while that from the AG l-X10 was only 85 per cent. The HCI concentration of the eluant has no effect on the @Ga elution between 0-l N and 1.0 N. However, with appreciably higher acid concentrations, the recovery of the 6*Ga falls drastically. The height of
45
the column (between 2 and 8 cm) also has little effect on the ssGa recovery, but below 2 cm the column cannot retain the entire amount of 6*Ga added at the rapid rate used, and approximately 5-10 per cent of the activity passes through with the EDTA. The final eluate containing the ssGa has been tested for contamination by EDTA and aluminum (arising from the alumina support in the generator) with the calorimetric methods described by BRADY and GWILT(~)and SANDELL.~~)Total contamination by EDTA for any one separation run was less than 0.5 pg and that for A1+3 approximately 3 pg. Tests using USP techniques indicate that this separation technique introduces no pyrogens in the final product. The separation procedure requires approximately 15 min. Sterility tests would have to be made on the product from any further processing of the separated 8sGa. J. E. CARLTON R. L. HAYES Medical Division Oak Ridge Associated Universities* Oak Ridge, Term. 37830, U.S.A.
* Under contract with the United States Atomic Energy Commission. References A. 1. SCHAER L. R., ANGERH. 0. and GOTTSCHALK J. Am. med. Ass. 198,811 (1966). R. M., AN~REWSG. A., EDWARDSC. L. 2. KNISELEY and HAYESR. L. Radial c&n. N. Am. 7,265 (1969). 3. EDWARDSC. L. and HAYES R. L. J. nucl. Med. 10, 103 (1969). 4. EDWARIISC. L. and HAYESR. L. J. Am. med. Ass. 212, 1182 (1970). B., SWARTZENDRUBER D. C., 5. H&ES R. L., NELSON CA~LTONJ. E. and BYRD B. L. Science 167,289 (1970). HAYES R. L., CARLTONJ. E., BYRD B. L. and RAFTERJ. J. nucl. Med. 8, 302 (1967). GREENEM. W. and TUCKERW. D. ht. J. appl. Radiat. Isotopes 12, 62 (1961). SAITOK. and TSIJCHIMOTO M. J. inorg. nucl. Chem. 23, 71 (1961). BRADYG. W. F. and GWILTJ. R. J. a&l. Chem. 12, 79 (1962). 10. SANDELLE. B. Colorimetriz Determination of Traces of Metals, Vol. 3, p. 116. Inter-science, New York.