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`DETAILED DESCRIPTION OF THE INVENTION
`
`[020] The present invention provides improved sodium nonatitanate compositions, a
`method using the composition for recovery of 82Sr from irradiated targets, and a method using
`the composition for generating 82Rb. The sodium nonatitanate materials of the invention are far
`
`more selective at separating strontium from solutions derived from the dissolution of in-adiated
`target materials than current ion exchange resins used in· the production of 82Sr. The present
`
`invention reduces the number of processing steps required, and thus leads to a decrease in target
`processing times and a reduction in the cost of the 82Sr product. Waste generation and disposal
`
`are also decreased.
`
`[021] According to the present invention, synthetic conditions are adjusted to produce a
`material with improved properties more applicable to 82Sr processing. The sodium nonatitanate
`
`of the present invention has been found to have a very low affinity for rubidium in addition to an
`
`exceptionally high affinity for strontium, making it ideal for use as a replacement for the hydrous
`tin dioxide used in current 82Rb generators. Sodium nonatitanate materials of this type will both
`impmve the retention of 82Sr and lead to a safer, more effective 82Rb generator system for clinical
`
`applications.
`
`[022] Sodium nonatitanate, Na4 Ti90 20xH20, is an inorganic ion exchange material that
`has been used for the removal of 90Sr from neutral and alkaline nuclear wastes. The sodium
`
`nonatitanate of the present invention has a number of advantages over conventional organic ion
`
`exchange resins (e.g., Che lex 100) that include: very high selectivity for trace levels of strontium
`
`in the presence of molar concentrations of other ions at alkaline pH; very low affinity for
`
`rubidium; excellent radiation, chemical and thermal stability so that there is no release of
`contaminants (e.g., Ti) into the 82Rb product; rapid reaction kinetics; high cation exchange
`
`capacity; absorbed ions are readily stripped by treatment with dilute mineral acid allowing the
`
`sodium nonatitanate to be recycled, if desired; scale up of similar synthesis has already been
`
`demonstrated; and the sodium nonatitanate powder can be manufactured into pellets appropriate
`
`for column operations. Other chemically related sodium titanate materials suitable for use in the
`
`same manner as the aforementioned sodium nonatitanate (N~Ti9020xH20) include other titanate
`materials exhibiting high Sr affinity and low Rb affinity, including Sr-Treat (available from
`
`Selion Oy) and monosodium titanate (available from Boulder Scientific) It is also anticipated
`
`that analogous zirconates may exhibit similar properties.
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`[023] The invention also provides important improvements in the processing of
`irradiated targets to recover 82Sr. Sodium nonatitanate has a much greater affinity for 82Sr than
`
`currently used ion exchange resins, and a
`
`low affinity for other radioactive isotopes.
`
`Consequently, the use of sodium nonatitanate greatly simplifies the extraction process by
`reducing the number of separation steps that are required to produce chemically pure 82Sr. Thus,
`targets can be processed more rapidly and the recovery of 82Sr improved. Improved isotope
`
`selectivity may also facilitate the isolation of other useful isotopes from the targets, leading to
`
`greater payback from target processing operations.
`[024] Furthermore, less than 1 g of sodium nonatitanate material is needed in a 82Rb
`
`generator and 1 kg of this material is expected to be sufficient to process a large number of
`
`targets, even if the sodium nonatitanate material is not recycled and is disposed of after one use.
`
`Consequently, the additional cost incurred by the use of sodium nonatitanate will be negligible in
`comparison with the cost savings achieved in the 82Sr production.
`
`[025] It has been determined that replacing hydrous tin dioxide with sodium
`nonatitanate reduces the amount of 82Sr released during the operation of the 82Rb generator,
`thereby reducing the exposure of the patient to 82Sr. Sodium nonatitanate is also more
`
`chemically stable and less likely to leach non-radioactive contaminants into solution during
`
`operation of the generator. The sodium nonatitanate is also more amenable to recycling since the
`82Sr can readily be stripped with mineral acid without producing additional impmities.
`Recycling of 82Sr generators is already being used as a source of additional 82Sr, and
`
`improvements to the recycling procedure (obtained by using a superior ion exchange material)
`will facilitate the recovery of 82Sr from this source.
`
`[026] Although the sodium nonatitanate may be used as a direct replacement for
`hydrous tin dioxide in the 82Rb generator, it is also possible to use sodium nonatitanate in the
`form of a disposable add-on filter that could be used to trap any 82Sr that is leached from the
`generator during the production of 82Rb.
`[027] The first step in preparing a 82Rb generator is to load the parent 82Sr onto the
`
`sodium nonatitanate material and place the ion exchange material into a suitable column. It is
`essential that sufficient time be allowed for the 82Sr to be absorbed by the sodium nonatitanate
`
`material in order to maximize the loading of the parent radioisotope per gram of ion exchange
`
`material.
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`[028] For an 82Rb generator, the sodium nonatitanate may be loaded into the column and
`then loaded with 82Sr although this method results in depositing a disproportionate amount of the
`82Sr at the top of the column with the remainder of the column remaining as a guard bed to
`collect any 82Sr that migrates down the column. Alternatively, the sodium nonatitanate may be
`loaded with 82Sr before being placed in an ion exchange column to avoid preferentially loading
`the 82Sr on the top of the ion exchange. A high concentration of radioactivity on a very small
`
`volume of sodium nonatitante may result in undesirable radiolytic problems. Although sodium
`
`nonatitanate has been shown to be highly resistant to radiation damage, it is always considered
`
`prudent to avoid any unnecessary radiation exposure.
`In the medical field, use of the 82Rb generator preferably provides a saline solution
`
`[029]
`
`that can be intravenously injected into a patient as an imaging agent at a pH of between about 4.5
`and about 7. To achieve the desired pH range of the eluted 82Rb solution, a neutralization step
`
`may be performed on the sodium nonatitanate to lower the pH of the sodium nonatitanate. An
`82Rb generator having sodium nonatitanate that has not been neutralized to a lower pH produces
`an 82Rb eluate solution having a higher pH than is desired for an injectable pharmaceutical in the
`
`medical field. For example, using a normal saline eluant having an initial pH of about 7.6 to
`elute 82Rb from an 82Rb generator having sodium nonatitanate that has not been neutralized to a
`lower pH can produce an eluate with a pH as high as 9.5. Even though over time the pH of the
`
`eluate slowly declines as more eluant is run through the generator, it is preferable and more
`efficient that the 82Rb eluate produced from the generator is immediately suitable for medical
`
`use. In one experiment, it was determined that a 2.92 g alkaline nonatitanate column required
`
`about 44 L of pH 6.2 saline eluant throughput to lower the pH level of the eluate to within the
`desired pH range. However, the use of such a high volume of eluant before the 82Rb solution is
`
`produced at a desired pH level is unacceptable.
`
`[030] The neutralization step added to the nonatitanate synthesis effectively lowers the
`pH of the ion exchanger and provides an 82Rb solution having the desired pH range from the first
`
`use of the generator. The neutralization step includes adding an acid to the final stage of the
`
`nonatitanate synthesis. This neutralization step has no significant effect on the high separation
`factor that the nonatitanate possesses for strontium and rubidium as required for use in an 82Rb
`
`generator. However, using the sodium nonatitanate that has been neutralized to a lower pH
`results in an 82Rb product having an acceptable pH difference of less than one pH unit between
`
`the eluant and the eluate.
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`[031] The neutralization step includes resuspending the sodium nonatitanate product in
`
`a liquid and then adding an acid to lower the pH to between about 7 and about 9, preferably
`
`between about 7.2 and about 8.5. The pH is more preferably lowered to between about 7.5 and
`
`about 8.3 and most preferably to between about 7 .8 and about 8.2. Sodium nonatitanate is
`
`partially neutralized by contacting the sodium nonatitanate product with the acidic liquid. The
`
`product may be centrifuged, the supernatant poured off, and, if desired, the process repeated to
`
`neutralize the sodium nonatitanate product again to obtain the target pH. The liquid may be any
`
`suitable liquid such as normal saline, dilute sodium chloride, water or preferably, deionized
`
`water. Any strong acid may be added to lower the pH such as, for example, nitric acid, sulfuric
`
`acid, or preferably hydrochloric acid.
`
`[032] It is important to maintain the pH of the sodium nonatitanate above a minimum
`
`pH during the neutralization step because lowering the pH below neutral also lowers the
`
`separation efficiency of Sr/Rb. There is a correlation shown in between pH and the uptake of
`both 85Sr and 82Rb. At high pH, the uptake of 85Sr is high while the uptake of 82Rb is low. At
`pH between about 6 and about 7, the uptake of 85Sr starts to decrease while the uptake of 82Rb
`remains the same or slightly increases. At pH values lower than about 4, the affinity for 85Sr
`
`decreases dramatically.
`
`[033] As the pH of the equilibrium saline solution passing through the column
`
`increases, the nonatitanate affinity for the strontium increases while the affinity for the rubidium
`
`decreases. Therefore, lowering the pH of the produced nonatitanate by performing a neutralizing
`
`step at the end of the method of producing the nonatitanate results in generator having a shorter
`
`life. To optimize the life time and separation efficiency, either the neutralization step may be
`
`omitted or a less complete neutralization step may be performed to achieve a lesser degree of
`
`neutralization.
`
`[034] Optionally, an adjustment may be made to the pH of the eluate product obtained
`
`from the nonatitanate column that was produced without a neutralization step or was only
`
`slightly neutralized during the neutralization step. If the eluate product from the generator has a
`
`pH above the desired range, the pH of the eluate product may be decreased to the desired pH
`
`range by adding an acid. Acceptable acids include any acid suitable for neutralizing the eluant
`
`without rendering the neutralized eluant unsuitable for injection into a patient during a medical
`
`procedure as known by those having ordinary skill in the art. Suitable acids woul~ include, for
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`example, hydrochloric acid (HCl) and acetic acid (CH3COOH). HCl is preferred because the salt
`
`produced by the neutralizing reaction is NaCl, which is already present in the solution.
`
`[035] The acid may be added automatically to adjust the pH or the acid may be added
`
`manually. A pH meter preferably measures the pH of the eluate product. Alternatively, other
`
`means, such as pH indicating strips, may be used to measure the pH of the eluate. Preferably a
`
`pH meter monitors the pH of the eluate as the acid is added to obtain the eluate target pH of
`
`between about 4.5 and about 7. The acid may be added using a gravity system to drip or pour the
`
`acid into the eluate. Alternatively, a pressure system, such as a syringe, a pump or a gas
`
`pressurized system may be used to add the acid to the eluate. When the acid is added
`
`automatically, a controller monitors the output signal from a pH meter and adjusts a valve or a
`
`pump rate to add the amount of acid necessary to obtain the eluate target pH. If adjusted
`
`manually, acid may be added to the eluate by an operator, preferably in pre-packaged amounts,
`
`until a pH meter or indicator strip indicates that the target pH has been achieved. Preferably, the
`
`acid is added automatically to the eluate as the eluate flows from the column.
`
`[036] The size of the sodium nonatitanate particles used in the generator is an important
`
`factor. The use of large particles of sodium nonatitanate in a column provides low flow
`
`resistance of the eluant through the column but large particles cannot be packed into a column or
`
`elutable container as densely as smaller particles may be packed. Furthermore, large particles
`create long diffusion paths over which the 82Rb generated by the decay of 82Sr atoms located
`In
`
`deep in the particle must travel while diffusing from the centers of the large particles.
`
`contrast, fine particles of sodium nonatitanate permit more material to be packed into a column
`
`of a given volume and provide shorter diffusion paths out of the particles, but the fine particles
`produce greater flow resistance to the eluant during the elution of the 82Rb from the generator.
`[03 7] Therefore, the 82Rb generator preferably includes smaller particles of sodium
`
`nonatitanate because the shorter diffusion path allows the particles to equilibrate with the eluant
`
`more quickly and because the smaller particles pack more densely into a column of a given size.
`Both of these factors together promote the elution of 82Rb using a small volume of saline solution
`as the eluant and obtaining a high concentration of 82Rb in the eluate. Preferably, the particles of
`
`sodium nonatitanate are made as small as possible without causing excessive back pressure from
`the flow of the eluant through the column. Preferably, the size of the particles used in the 82Rb
`
`generator range between about 50 µm and about 200 µm. More preferably, the particle size of
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`the sodium nonatitanate is between about 75 and about 150 µm and most preferably between
`
`about 7 5 and about 100 µm.
`
`[038] Low porosity is a preferred characteristic of the sodium nonatitanate particles for
`use in the 82Rb generator of the present invention. If the particles are highly porous, much of the
`parent 82Sr deposits within the pores, which creates a longer diffusion path for the 82Rb to diffuse
`from the pores into the saline eluant. The 82Rb generated from the 82Sr deposited deep within a
`
`pore continues to decay while diffusing from the pore into the eluant stream, which results in a
`loss of the generated 82Rb and thereby, a lower 82Rb yield.
`
`[039] The column aspect ratio is a factor that contributes to the optimum operation of
`the 82Rb generator of the present invention. The aspect ratio of a column is the column length
`
`over the column diameter. Increasing column length at constant diameter provides for greater
`retention of 82Sr and thereby minimizes the amount of leached 82Sr in the final eluate product.
`However, as the column length increases, total pressure drop through the column increases,
`
`causing higher back pressure at the inlet to the column. The column aspect ratio affects the
`properties of the 82Rb generator even at constant column volume and sodium nonatitanate mass.
`
`[040] A long, narrow column having a high aspect ratio offers greater resistance to the
`
`flow of the eluant and generates a higher backpressure at the inlet to the column. Because the
`
`velocity of a given volume of eluant is higher in a column having a high aspect ratio, the flow
`
`through the column having a high aspect ratio is more turbulent, which increases mixing within
`
`the eluant stream. Comparatively, a short, wide column having a low aspect ratio operates with a
`
`lower velocity of a given volume of eluant through the column and operates at lower pressure
`
`drop with less mixing. However, channeling through the bed can occur at low velocities
`
`resulting in the eluant bypassing some of the ion exchange material and providing a lower yield.
`
`While a wide range of column aspect ratios are acceptable, preferably, without limitation, the
`
`aspect ratio may be between about 4 and 50, more preferably between about 6 and about 20.
`
`[041] Preferably, the column or other elutable container is not loaded with uniform
`
`material over its entire length. The portion of the column closest to the generator outlet
`preferably holds sodium nonatitanate containing no 82Sr, serving as a guard bed to intercept any
`82Sr or 85Sr released from the generator. By intercepting and capturing any released 82Sr and 85Sr,
`the product eluant is safe for use as an 82Rb tracer. The guard bed may be formed with sodium
`
`nonatitanate that was produced without the neutralization step so that the affinity to capture
`
`strontium is at its highest level and the affinity to capture rubidium is at its lowest level.
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`Optionally, the guard bed may be placed in a second separate container, receiving the eluate from
`the outlet of the generator, to filt~ any strontium from the eluant eluted from the 82Rb generator.
`Alternatively, a guard bed may be installed in the generator as described above coupled with a
`
`separate filter containing sodium nonatitanate as an added precaution.
`
`[042] Optionally, the sodium nonatitanate may be supported on the surface of a non(cid:173)
`
`porous support. Placing the sodium nonatitanate in a thin layer on a non-porous support provides
`
`the advantage of placing all of the sodium nonatitanate in close contact with the eluant, thereby
`minimizing the length of the diffusion path of the 82Rb from the nonatitanate to the eluant.
`
`Suitable non-porous support materials include inorganic materials that are not damaged in a high
`
`radiation field, such as fiberglass, fine glass beads, ceramics, and other similar materials known
`
`to those skilled in the art. It is critical that any material chosen for this function does not release
`
`anything into the eluate that could contaminate the product.
`[043] The examples that follow disclose the methods and materials for the 82Rb
`
`generator. Examples 12-18 further disclose the nonatitanate neutralized to a lower pH for
`
`providing an eluate having a pH within the desired range.
`
`EXAMPLES
`
`[044] These Examples investigated the suitability of sodium nonatitanate for the use in
`separating 82Sr from irradiated targets and in the construction of an 82Sr/82Rb generator. Initial
`
`batch experiments compared the rubidium and strontium selectivities of a number of different
`
`sodium nonatitanate samples with commercially available ion exchange materials (e.g., AW 500,
`
`Chelex 100) and some experimental materials that had also exhibited high strontium selectivities
`
`(e.g., sodium titanosilicate). Column experiments were then performed using target simulants
`
`and generator simulants on materials that exhibited favorable selectivity characteristics. Some
`
`work was also performed to investigate the likely interference from other isotopes present in
`irradiated targets on the production of 82Sr.
`
`Example 1 - Preparation of Sodium Nonatitanate
`
`[045] Sodium nonatitanate (NaTi) was synthesized hydrothermally as follows. 77.5 g of
`
`titanium isopropoxide was added to 84.35 g of a 50 wt% solution ofNaOH with vigorous stirring
`
`and 60 mL of deionized water was added. The resultant gel was heated at approximately 108 °C
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`for 3 hours, transferred to a hydrothermal pressure vessel with an additional 90 mL of deionized
`
`water, and heated at either 170 °C or 200 °C for times ranging :from 21 hours to 1 week. After
`
`the allotted time, the materials were filtered, washed with .ethanol to remove residual base and
`
`dried at 60 °C. The mass of sodium nonatitanate prodU:?ed was approximately 31 g. Each
`
`sample was characterized using x-ray powder diffractiofr (XRD). The reaction is outlined in
`
`Equation 1.
`
`[046] The crystallinity of the material was shgwn to be dependent upon the reaction
`
`time and temperature, with the most crystalline materials being produced after 1 week of
`
`hydrothermal treatment (200 °C for 7 days). Samples that received no hydrothermal treatment, or
`
`only a few days, were virtually amorphous with only a few very broad reflections visible on the
`
`XRDpattem.
`
`[047] The theoretical cation exchange capacity (CEC) of sodium nonatitanate is quite
`
`high and has a value of 4.74 meq/g, which compares favorably with organic ion exchange resins.
`
`[048] Alternative titanium salts that could be used to manufacture sodium nonatitanate
`
`include titanium tetrachloride, TiC14, and titanium sulfate, TiOS04.xH2S04.yH20. However,
`hydrolysis of these salts leads to the generation of hydrochloric acid and sulfuric acid,
`
`respectively, and thus additional base is required to neutralize the acids during the hydrothermal
`
`process. The final product also needed to be exhaustively washed to remove residual sodium
`
`chloride or sodium sulfate. Consequently, titanium isopropoxide (which hydrolyzes to form
`
`propanol) or titanium dioxide Ti02 is the preferred starting material because the final product is
`
`:free :from additional sodium salts.
`
`Example 2 - Determination of Strontium Selectivity
`
`[049] Sodium nonatitanate and a variety of other ion exchange materials were obtained
`and evaluated for use in the separation of 82Sr :from targets and in a 82Rb generator. These
`
`materials are described below in Table 1.
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`aena s va uate d. h" s d
`a e -
`on xc ange Mt . I E 1
`T bl 1 Ch aractenstics o fl E h
`
`1ll t IS
`tu lY
`Source
`Material
`GSA Resources, AZ,
`Na-Clinoptilolite
`Aldrich (1.6 mm Pellets)
`AWSOO
`Synthesized in house
`Hydrous Sn02
`
`K + Pharmacosiderite
`(K3H(TiO)iSi04)3.4H20)
`Sodium Titanosilicate
`(Na2Ti203Si04.2H20)
`AG 50W-X8 (Na+)
`(25 - 50 Mesh)
`Chelex 100 (Na+)
`(50 - 100 Mesh)
`Sodium Nonatitanate
`Hydrous Si02
`
`Synthesized according to literature
`method
`Synthesized according to literature
`method
`BioRad. Strong acid ion exchange
`resin.
`BioRad. Chelating resin with
`iminodiacetic acid functionality
`Honeywell, IL
`Synthesized in house
`
`Hydrous Ti02
`
`Hydrous Zr02
`
`Synthesized in house
`
`Synthesized in house
`
`Sample Preparation
`Ground to powder.
`Ground to powder
`NaOH + SnC14 . Washed with
`acetic acid/sodium acetate buffer
`None. Used as synthesized
`
`None. Used as synthesized
`
`Converted to Na+ form
`(for alkaline solutions only)
`None. Used as received
`
`None. Used as received
`Acetic acid hydrolysis of
`tetraethyl orthosilicate. Washed
`withH20
`Hydrolysis of titanium
`isopropoxide. Washed with H20
`ZrOClz + NaOH. Washed with
`deionized water
`
`[050] The strontium selectivity of the ion exchange materials of Table 1 was evaluated
`
`in sodium chloride and rubidium chloride solutions using radiotracer techniques. Samples were
`
`evaluated using a simple batch teclmique to allow the rapid screening of a large number of
`
`materials over a range of ionic strengths. Blanks were run for each matrix to check for any loss
`
`of strontium during filtration or absorption of strontium onto the scintillation vials.
`
`In all
`
`solutions evaluated, strontium absorption was negligible.
`
`[051] 0.05 g of each of the ion exchange materials was contacted with 10 mL of a
`solution, spiked with 89Sr, in a capped scintillation vial.
`
`(The total strontium content was
`
`approximately 1.6 ppm, thus preventing any loss of strontium in solution due to precipitation of
`
`sparingly soluble Sr(OH)2 at alkaline pH values.) The mixtures were shaken for 6 hours, filtered
`
`through a 0.2 µm syringe filter and the residual activity determined using liquid scintillation
`
`counting (LSC). Distribution Coefficients (K<I values) were then determined according to
`
`Equation 2:
`
`Ki= (Ai -Ar) I Ar* V/m
`
`(2)
`
`where: Ai= initial activity in solution (counts per minute (cpm)/mL)
`
`Ar= final activity in solution ( cpm/mL)
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`V =volume of solution (mL)
`
`m = mass of exchanger (g)
`
`[052] The final pH of the solution was also noted. The period of 6 hours was chosen to
`
`allow equilibrium to be reached for each of the ion exchange materials. However, previous work
`
`on the titanosilicates and titanates had shown the reaction rates to be rapid with the majority of
`
`the uptake occurring in only a few minutes. The concentration of the chloride solutions was
`
`varied from lM to O.OOlM to evaluate the effect of increasing Rb+ and Na+ concentrations on the
`uptake of Sr2+. All experiments were performed in duplicate, and if significant variations
`
`between duplicate samples occurred, the experiments were repeated until good agreements on the
`l«) values were obtained. The results are shown in Tables 2 and 3 and represented the average Ket
`
`obtained, quoted to 3 significant figures.
`
`Table 2 - Strontium Selectivity Data from Unbuffered Sodium Chloride Solutions
`
`Ion Exchange Material
`
`Na-Clinoptilolite
`AW500
`Hydrous Sn02
`K + Pharmacosiderite
`Sodium Titanosilicate
`AG50W(Na+)
`Chelex 100 (Na+)
`NaTi (Honeywell)
`NaTi (No hydrothermal)
`NaTi (l 70°C, 2lhr)
`NaTi (l 70°C, 3d)
`NaTi (170°C, 7d)
`NaTi (200°C, 2lhr)
`NaTi (200°C, 3 d)
`NaTi (200°C, 7d)
`Zr02
`
`K.tmUg
`lMNaCI
`8
`1,860
`767
`18,300
`556,000
`32
`610
`80,600
`1,530,000
`1,030,000
`959,000
`167,000
`439,000
`261,000
`195,000
`3,360
`
`O.lMNaCl
`124
`88,300
`43,000
`251,000
`273,000
`3,380
`26,400
`1,030,000
`2,570,000
`1,240,000
`633,000
`834,000
`1,390,000
`898,000
`955,000
`52,200
`
`O.OlMNaCl
`3,260
`1,270,000
`124,000
`594,000
`119,000
`365,000
`726,000
`258,000
`739,000
`272,000
`218,000
`264,000
`197,000
`251,000
`265,000
`213,000
`
`O.OOlMNaCl
`36,900
`1,210,000
`51,800
`281,000
`42,900
`2,510,000
`1,300,000
`166,000
`372,000
`172,000
`93,100
`90,400
`120,000
`158,000
`214,000
`232,000
`
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`Table 3 - Strontium Selectivity Data from Unbuffered Rubidium Chloride Solutions
`
`Material
`
`Na-Clinoptilolite
`AW500
`Hydrous Sn02
`K + Pharmacosiderite
`Sodium Titanosilicate
`AG-SOW (Na+)
`Chelex 100 (Na+)
`NaTi (Honeywell)
`NaTi (No hydrothermal)
`NaTi (170°C, 21hr)
`NaTi (170°C, 3d)
`Na Ti ( 170°C, 7 d)
`NaTi (200°C, 2 lhr)
`NaTi (200°C, 3 d)
`NaTi (200°C, 7d)
`Zr02
`
`Krt mL/g
`lMRbCI O.lMRbCI O.OlMRbCI
`19
`3
`88
`9,750
`107,000
`1,020,000
`66,100
`766
`104,000
`1,950
`40,800
`419,000
`12,600
`94,700
`164,000
`3,870
`237,000
`44
`38,400
`1,580
`555,000
`108,000
`13,900
`279,000
`116,000
`14,220
`345,000
`71,700
`10,500
`193,000
`15,100
`39,500
`68,000
`23,000
`55,800
`31,200
`66,400
`11,000
`110,000
`56,800
`146,000
`10,600
`57,400
`146,000
`10,500
`3,000
`42,400
`184,000
`
`O.OOlMRbCI
`11,000
`1,280,000
`51,800
`427,000
`179,000
`800,000
`977,000
`324,000
`429,000
`205,000
`95,200
`110,000
`103,000
`158,000
`158,000
`221,000
`
`[053] Comparing the selectivity data from sodium and rubidium solutions, it is evident
`
`that rubidium ions cause a reduction in affinity for the strontium ion for all of the exchangers
`
`indicating that the affinity of these materials for rubidium is significantly higher than the affinity
`
`for sodium ions. The pH of the final solutions was generally alkaline for the nonatitanates
`
`(NaTi) and titanosilicates, with pH values as high as 12 being measured. This was due to
`
`hydrolysis of the exchangers resulting in the absorption of protons and the release of sodium
`
`ions, thus increasing the pH of the aqueous phase. This effect can be overcome, if desired, by
`
`buffering the solution.
`
`[054] The most distinct trend was observed in lM NaCl solutions for the sodium
`nonatitanate samples. The highest Kc! was observed for the non-hydrothermal material and the
`~ values decreased with increasing reaction time for both the 200 °C and 170 °C materials.
`
`Clearly, strontium uptake is facilitated by having a low-crystallinity material. This suggests that
`
`as the crystallinity increases and the size of the nonatitanate crystallites also increases, it becomes
`
`thermodynamically less favorable for exchange of the sodium ions by strontium.
`
`It is also
`
`interesting to note that the majority of the sodium nonatitanates exhibit a higher selectivity for
`
`strontium in lM NaCl than in O.OOlM NaCL This indicates that the higher ionic strength
`facilitates the Na+/Sr2+ exchange reaction and more than compensates for the increased
`
`competition for the ion exchange sites from the additional Na+ ions.
`
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`
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`
`[055] This data shows that sodium nonatitanate is an ideal material for the recovery of
`82Sr from irradiated rubidium and rubidium chloride targets and in the manufacture of a 82Rb
`
`generator.
`
`Example 3 - Rubidium Selectivity from NaCl Solutions
`[056] For an ion exchange material to be suitable for use in a 82Rb generator, it must
`have a very high selectivity for strontium to prevent any loss of 82Sr from the ion exchange
`
`column and release to the patient undergoing a PET scan. This propelty was clearly
`
`demonstrated in Example 2. It must also have a very low selectivity towards rubidium, thus
`allowing 82Rb to be released into solution as saline is passed through the 82Rb generator.
`
`Consequently, the rubidium selectivity of the ion exchange materials was evaluated in sodium
`
`chloride media following the procedure described in Example 2. The same procedure was
`followed using 86Rb to spike the solutions to give an activity of approximately 200,000 cpm/mL.
`Total rubidium in solution was < 0.05 ppm. The distribution coefficients of the materials are
`
`shown below in Table 4.
`
`- u 1 mm e ectiv1ty ata om nu ere
`fr U b f:D
`.
`.d S I
`Chl
`d S d.
`. . D
`S 1
`T bl 4 R b.d.
`o mm
`on e o ut10ns
`a e
`Ion Exchan2e Material
`lMNaCI
`O.lMNaCI
`O.OlMNaCI
`AW500
`116
`620
`4920
`Hydrous Sn02
`1
`6
`36
`K + Phannacosiderite
`148
`475
`2030
`8,010
`194,000
`Sodium Titanosilicate
`114000
`AG50W(Na+)
`7
`75
`688
`Chelex 100 (Na+)
`3
`8
`43
`NaTi (Honeywell)
`102
`488
`9
`NaTi (No hydrothermal)
`4
`59
`280
`NaTi (170°C, 21hr)
`209
`56
`9
`46
`NaTi (1700C, 3d)
`7
`198
`NaTi (170°C, 7d)
`15
`3
`47
`NaTi (200°C, 21hr)
`79
`8
`334
`NaTi (200°C, 3d)
`52
`207
`8
`NaTi (200°C, 7d)
`25
`111
`4
`12
`Zr02
`60
`1
`
`O.OOlMNaCI
`21900
`290
`4020
`75800
`6680
`256
`817
`446
`297
`311
`71
`502
`307
`178
`154
`
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`
`trontmm-Ru idium s eparat10n F actor
`T bl A S a e4 -
`
`
`b
`lMNaCI
`Ion Exchant?:e Material
`16.0
`AW500
`767
`Hydrous Sn02
`K + Pharmacosiderite
`124
`69.4
`Sodium Titanosilicate
`4.57
`AG50W(Na+)
`Chelex 100 (Na+)
`203
`NaTi (Honeywell)
`8,956
`NaTi (No hydrothermal)
`382,500
`NaTi (170 C, 2lhr)
`114,444
`NaTi (170 C, 3d)
`137,000
`NaTi (170 C, 7d)
`55,667
`NaTi (200 C, 21hr)
`54,875
`32,625
`NaTi (200 C, 3d)
`NaTi (200 C, 7d)
`48,750
`Zr02
`3,360
`
`O.lMNaCI
`142
`7,167
`528
`1.41
`45.1
`3,300
`10,098
`43,559
`22,143
`1,370
`55,600
`17,595
`17,269
`38,200
`4,350
`
`O.OlMNaCI
`258
`3,444
`293
`1.04
`531
`16,884
`529
`2,639
`1,301
`1,101
`5,617
`590
`1,213
`2,387
`3,550
`
`O.OOlMNaCI
`55.3
`179
`69.9
`0.57
`376
`5,078
`203
`834
`579
`299
`1,273
`239
`515
`1,202
`1,506
`
`Table 4B - Percent Rubidium Retention Generated on 0.1 g of Exchanger in NaCl Solution
`lMNaCI
`O.lMNaCI
`Ion Exchan2e Material
`O.OlMNaCI
`O.OOlMNaCI
`AWSOO
`18.8
`55.4
`90.8
`97.8
`Hydrous Sn02
`0.2
`1.2
`6.7
`36.7
`K + Pharmacosiderite
`22.8
`48.7
`80.2
`88.9
`Sodium Titanosilicate
`94.1
`99.7
`99.6
`99.3
`AGSOW(Na+)
`1.4
`13.0
`57.9
`93.0
`Chelex 100 (Na+)
`0.6
`1.6
`7.9
`33.9
`NaTi (Honeywell)
`1.8
`16.9
`62.0
`49.4
`10.6
`N aTi (No hydrothermal)
`0.8
`35.9
`47.1
`NaTi (170 C, 21hr)
`10.1
`29.5
`1.8
`37.3
`NaTi (170 C, 3d)
`1.4
`8.4
`28.4
`38.3
`NaTi (170 C, 7d)
`0.6
`2.9
`8.6
`12.4
`NaTi (200 C, 2lhr)
`1.6
`13.6
`40.0
`50.1
`NaTi (200 C, 3d)
`1.6
`9.4
`29.3
`38.0
`4.8
`NaTi (200 C, 7d)
`0.8
`18.2
`26.3
`2.3
`Zr02
`0.2
`10.7
`23.5
`
`[057] From the data in Table 4, it is clear that the all of the sodium nonatitanate
`
`materials have a very low affinity for rubidium, particularly in the presence of relatively high
`
`amounts of sodium ions. In general, the rubidium selectivity decreased with increasing reactio