`
`US 2007 O140958A1
`
`(19) United States
`(12) Patent Application Publication (10) Pub. No.: US 2007/0140958 A1
`deKemp
`(43) Pub. Date:
`Jun. 21, 2007
`
`(54) RUBIDIUM GENERATOR FOR CARDIAC
`PERFUSION MAGING AND METHOD OF
`MAKING AND MANTAINING SAME
`
`(75)
`
`Inventor: Robert A. deKemp, Ottawa (CA)
`
`Correspondence Address:
`OGLVY RENAULT LLP
`1981 MCGILL COLLEGE AVENUE
`SUTE 16OO
`MONTREAL, QC H3A2Y3 (CA)
`
`(73)
`
`Assignee: Ottawa Heart Institute Research Cor
`poration, Ottawa (CA)
`
`(21)
`(22)
`
`Appl. No.:
`
`11/312,368
`
`Filed:
`
`Dec. 21, 2005
`
`Publication Classification
`
`(51) Int. Cl.
`(2006.01)
`A6II 5L/00
`(2006.01)
`G2G L/06
`(52) U.S. Cl. ........................................... 424/1.11: 376/185
`(57)
`ABSTRACT
`An SrfRb generator column is made using a fluid imper
`vious cylindrical container having a cover for closing the
`container in a fluid tight seal, and further having an inlet for
`connection of a conduit for delivering a fluid into the
`container and an outlet for connection of a conduit for
`conducting the fluid from the container. An ion exchange
`material fills the container, the ion exchange material being
`compacted within the container to a density that permits, the
`ion exchange material to be eluted at a rate of at least 5
`ml/min at a fluid pressure of 1.5 pounds per square inch (10
`kPa). The generator column can be repeatedly recharged
`with Sr. The generator column is compatible with either
`three-dimensional or two-dimensional positron emission
`tomography systems.
`
`
`
`Calibration?
`Patient Elution
`(at least
`10 ml/min
`at 3 psi)
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`JUBILANT EXHIBIT 1034
`Jubilant v. Bracco, IPR2018-01449
`
`

`

`Patent Application Publication Jun. 21, 2007 Sheet 1 of 4
`
`US 2007/O140958A1
`
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`

`

`Patent Application Publication Jun. 21, 2007 Sheet 2 0f 4
`
`US 2007/0140958 A1
`
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`Patient Elution
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`

`Patent Application Publication Jun. 21, 2007 Sheet 3 of 4
`
`US 2007/O140958A1
`
`
`
`
`
`
`
`Prepare ion exchange material and
`pack generator column
`
`200
`
`Condition generator column and
`perform non-destructive pH test
`
`202
`
`
`
`Dispose of generator
`column
`
`224
`
`L - - - - - - -
`
`fe
`|Flush generator
`|coluntand test
`eluate for: trace
`metals; sity,
`radignuclide
`Ery pyrogens;
`218.
`
`
`
`3 Alkaline pH2
`
`
`
`Load generator
`column with 82Sr
`
`
`
`Flush generator column and test eluate for:trace
`metals; sterility; radionuclide purity; pyrogens; pH
`
`
`
`1 pre-use testss
`passed? .
`
`Generator column ready for use
`and daily testing
`
`
`
`
`
`
`
`All daily tests
`passed?
`
`
`
`
`
`Reload permitsg?
`
`

`

`Patent Application Publication Jun. 21, 2007 Sheet 4 of 4
`
`US 2007/O140958A1
`
`Begin Use
`
`
`
`
`
`Flush generator column with
`sterile saline, and Compute
`Cumulative volume
`
`Wait predetermined time
`
`3OO
`
`Perform calibration elution and
`C End D 322 Compute cumulative volume
`firin,
`Return generator al
`column for reload and
`pre-use testing
`320
`1's
`13 Reload # < limit?)--N
`s N
`
`Test eluate for Rb yield
`and Sr breakthrough
`
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`
`
`
`1
`
`n
`
`N
`
`e
`
`
`
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`
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`
`
`
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`breakthrough
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`
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`
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`
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`
`
`
`-
`Curnulative
`olume < limit
`
`
`
`
`
`
`
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`
`Y
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`compute cumulative volume:
`
`
`
`
`
`
`
`318
`
`.
`
`...
`
`,
`
`Date changed
`314
`
`

`

`US 2007/O 140958 A1
`
`Jun. 21, 2007
`
`RUBDIUM GENERATOR FOR CARDAC
`PERFUSION MAGING AND METHOD OF
`MAKING AND MANTAINING SAME
`
`CROSS-REFERENCE TO RELATED
`APPLICATIONS
`0001. This is the first application filed for the present
`invention.
`
`MICROFICHEAPPENDIX
`0002) Not Applicable.
`
`TECHNICAL FIELD
`0003. The present application relates in general to nuclear
`medicine and, in particular, to a rubidium generator for
`cardiac perfusion imaging and method of making and main
`taining same.
`
`BACKGROUND OF THE INVENTION
`0004) As is well known in the art, Rb is used as a
`positron emission tomography (PET) tracer for measure
`ment of myocardial perfusion (blood flow) in a non-invasive
`a.
`0005 Recent improvements in PET technology have
`introduced 3-dimensional positron emission tomography
`(3D PET). Although 3D PET technology may permit more
`efficient diagnosis and prognosis in patients with Suspected
`coronary artery disease, the sensitivity of 3D PET requires
`very accurate control of the delivery of R activity to a
`patient being assessed.
`0006) As is well understood in the art, Rb for myocar
`dial perfusion imaging is produced using a strontium-ru
`bidium (SrfRb) generator which is eluted using a sterile
`saline solution (0.9% Sodium Chloride Injection) to produce
`an Rb eluate (Rb Rubidium Chloride Injection) that is
`injected into the patient during the PET imaging. Due to the
`above-noted sensitivity of 3D PET it is desirable to deliver
`the Rb elution to the patient as far away from the patient’s
`heart as can be practically achieved. This is best accom
`plished by using a small vein in the patient's hand, for
`example, as the Rb elution injection site. Doing so, how
`ever, requires a low pressure, low flow rate elution and
`precision flow control.
`0007) There therefore exists a need for an Rb generator
`that enables low pressure elution and facilitates precision
`flow control of patient elution injections.
`
`SUMMARY OF THE INVENTION
`0008. It is therefore an object of the invention to provide
`a rubidium generator column that enables low pressure
`elution and facilitates precision flow control of patient
`elutions.
`0009. The invention therefore provides a method of pre
`paring an Sri Rb generator column for low pressure
`elution, comprising: filling the generator column with an ion
`exchange material that tightly binds Sr but not Rb, and
`compacting the ion exchange material to a density that
`permits fluid solutions to be pumped through the generator
`column at a rate of at least 5 ml/min at a fluid pressure of 1.5
`
`pounds per square inch (10 kPa); conditioning the ion
`exchange material; and loading the generator column with a
`solution of Sr.
`0010) The invention further provides an SrfRbgen
`erator column, comprising: a fluid impervious cylindrical
`container having a cover for closing the container in a fluid
`tight seal, and further having an inlet for connection of a
`conduit for delivering a fluid into the container and an outlet
`for connection of a conduit for conducting the fluid from the
`container, and anion exchange material filling the container,
`the ion exchange material being compacted within the
`container to a density that permits the ion exchange material
`to be eluted at a rate of at least 5 ml/min at a fluid pressure
`of 1.5 pounds per square inch (10 kPa).
`
`BRIEF DESCRIPTION OF THE DRAWINGS
`0011 Further features and advantages of the present
`invention will become apparent from the following detailed
`description, taken in combination with the appended draw
`ings, in which:
`0012 FIG. 1 is a schematic diagram illustrating the
`packing of a generator column in accordance with the
`invention;
`0013 FIG. 2 is a schematic diagram of the generator
`column shown in FIG. 1 Suspended in a shielding body and
`being loaded with Sr.
`0014 FIG. 3 is a schematic diagram of the generator
`column shown in FIG. 1 configured for calibration and
`patient elutions;
`0015 FIG. 4 is a flowchart illustrating the method in
`accordance with the invention for making the generator
`columns shown in FIGS. 1-3; and
`0016 FIG. 5 is a flowchart illustrating principle steps in
`the use of the generator column shown in FIG. 3.
`0017. It will be noted that throughout the appended
`drawings, like features are identified by like reference
`numerals.
`
`DETAILED DESCRIPTION OF THE
`PREFERRED EMBODIMENT
`0018. The present invention provides an SrfRbgen
`erator column for use in positron emission tomography
`cardiac perfusion imaging. In accordance with the invention,
`the generator column is filled with an ion exchange material
`that tightly binds Sr but not Rb. The ion exchange
`material is compacted to a density that permits fluid solu
`tions to be pumped through the generator column at a rate of
`at least 5 ml/min at a fluid pressure of 1.5 pounds per square
`inch (10 kPa). After the generator column is packed with the
`ion exchange material, it is conditioned with a source of
`excess sodium cations and loaded with a solution of Sr.
`The generator column in accordance with the invention
`enables low pressure injections using a peristaltic pump and
`facilitates precision flow control of patient elutions. Advan
`tageously, the generator column in accordance with the
`invention can also be reloaded with Sr a plurality of times.
`This has distinct advantages. First, residue Sr remaining in
`the column from a previous load is not wasted. Second, the
`expense of building and conditioning the generator column
`
`

`

`US 2007/O 140958 A1
`
`Jun. 21, 2007
`
`is distributed over a plurality of Sr loads, so the overall
`cost of using, Rb for cardiac perfusion imaging is reduced.
`0019 FIG. 1 illustrates the packing of an Rb generator
`column 10 using a method in accordance with the invention.
`As is known in the art, the generator column 10 is con
`structed from stainless steel hardware components that are
`commercially available. In the embodiment shown in FIG.
`1, a pair of SWAGELOKR reducing adaptors with nuts and
`ferrules 12, 14 are connected to opposite ends of a stainless
`tubing 16 that is packed with an ion exchange material 18.
`In one embodiment of the invention, the ion exchange
`material 18 is an O-hydrous tin dioxide (SnoxH2O, where
`x equals 1-2) wetted with a NHOH/NHC1 buffer (pH 10).
`0020 A 25 micron filter 24 closes a bottom of the
`cylinder 16 at an outlet end thereof. Likewise, a 25 micron
`filter 22 closes an inlet end of the cylinder 16 after the
`cylinder 16 is packed with the ion exchange material 18. A
`feature of the invention is that, unlike prior art generator
`columns in which the ion exchange material is tightly
`packed so that high pressure elution is required, the ion
`exchange material 18 is packed only to a density that permits
`fluid solutions to be pumped through the generator column
`at a rate of at least: 5 ml/min at a fluid pressure of 1.5 pounds
`per square, inch (10 kPa). As shown in FIG. 1, a simple and
`practical way of accomplishing, the required packing of the
`ion exchange material 18 is to repeatedly strike a side of the
`generator column 10 with an instrument 26, Such as a
`laboratory wrench, with a force that exerts about 0.1 Joule.
`Experience has shown that between 50 and 100 strikes are
`required to achieve the required density of the ion exchange
`material 18.
`0021. After packing of the generator column 10 is com
`plete, a funnel 20 that was used to introduce the ion
`exchange material 18 into the cylinder 16 is removed and the
`ion exchange material is leveled with the top of the cylinder
`16. The ion exchange material packed into the generator
`column 10 has a density of not more than 3 g/cm in the
`packed state. The filter 22 is then placed on top of cylinder
`16 and the SWAGELOK adapter, nut and ferrule 12 is
`secured to the top of the cylinder in a manner well known in
`the art. As will be understood by those skilled in the art, the
`generator column 10 in accordance with the invention is
`constructed under Sterile conditions using sterile compo
`nents and may be pressure tested for leaks after assembly.
`0022 FIG. 2 is a cross-sectional view of the generator
`column 10 suspended in a shielding body 40. The shielding
`body 40 is made from a dense shielding material 42. Such as
`lead, tungsten or depleted uranium optionally encased in a
`stainless steel shell 44. The shielding body 42 includes a
`shielding lid 50 having apertures through which extend an
`inlet line 34 and outlet line 36. The inlet line 34 is connected
`to an inlet end 30 of the generator column 10. The outlet line
`36 is connected to an outlet end 32 of the generator column
`10. The inlet and outlet lines are connected to external tubing
`lines 60, 62 using Luer fittings 56 and 58. The shielding lid
`50 is likewise constructed of a shielding material 52 such as
`lead, tungsten or depleted uranium encased in a stainless
`Steel shell 54.
`0023. After the generator column 10 is packed with ion
`exchange material 18, as explained above with reference to
`FIG. 1, the generator column 10 must be loaded with Sr
`before patient elutions can begin. As Schematically illus
`
`trated in FIG. 2, in one embodiment a syringe pump 80 is
`used to deliver Sr from a supply 70 through an inlet tube
`60 to the generator column 10. The Sr is bound by the ion
`exchange material 18 in the generator column 10. Waste
`fluid is evacuated through the outlet tube 36 and outlet line
`62 to a shielded waste container 90, in a manner known in
`the art.
`0024 FIG. 3 is a schematic diagram of the generator
`column 10 configured for daily use as an Rb source for
`cardiac perfusion imaging. A source of sterile Saline Solution
`100 is connected to a saline supply tube 104. The sterile
`saline solution 100 is pumped through the saline supply tube
`104 by a pump 102. In one embodiment of the invention, the
`pump 102 is a peristaltic pump. In accordance with an
`alternate embodiment, the pump 102 is the syringe pump 80
`shown in FIG. 2.
`0025. As understood by those skilled in the art, the pump
`102 is controlled by a control algorithm that regulates a flow
`rate and volume of the sterile saline solution 100 pumped
`through the generator column 10 via the inlet tube 104 to
`provide an Rb eluate via an outlet tube 106 connected to
`a controlled valve 108. The valve 108 directs the eluate
`through a delivery line 112 for a calibration elution or a
`patient elution 110, or to a shielded waste container 90. As
`is further understood by those skilled in the art, control of the
`system shown in FIG. 3 is complex and not all of the fluid
`paths and control mechanisms are depicted because elution
`control is not a subject of this invention.
`0026 FIG. 4 is a flowchart illustrating principle steps in
`constructing the generator column 10 in accordance with the
`invention. The process begins by preparing the ion exchange
`material and packing the generator column as explained
`above with reference to FIG. 1 (step 200). The generator
`column is then conditioned by Saturating the ion exchange
`material 18 with sodium cations. In one embodiment, this is
`accomplished by passing 120 ml of 2M NaCl through the
`column at a flow rate of 0.5 ml/minute followed by waiting
`for a period of 12 hours. 500 ml of sterile saline solution is
`then passed through the column at a flow rate of 10
`ml/minute. A nondestructive pH test is performed (step 202)
`by testing a pH of the initial sterile saline solution passed
`through the column. This nondestructive pH test prolongs
`the life of the generator column 10.
`0027) If it is determined (step 204) that the pH of the
`generator column 10 is not alkaline, the generator column 10
`is defective and it is disposed of (step 224). If the saline
`solution is determined in step 204 to be alkaline, the
`generator column is loaded with Sr (step 206) in a manner
`well known in the art using the equipment briefly described
`above with reference to FIG. 3. After the Sr is loaded into
`the generator column 10, the generator column 10 is flushed
`with 1.0 L of sterile saline solution to clear traces of tin:
`dioxide and any radionuclide impurities. The generator
`column is then eluted with sterile saline solution and the
`eluate is tested for trace metals; sterility; radionuclide purity:
`pyrogens; and pH (step 208). If all of those tests are passed
`(step 210) the generator column 10 is ready for use (step
`212). If any one of the tests fails, Sr is optionally recovered
`from the generator column 10 (step 222) and the generator
`column 10 is disposed of (step 224).
`0028. During generator use, daily testing is performed for
`the purpose of patient safety and quality control, as will be
`
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`

`US 2007/O 140958 A1
`
`Jun. 21, 2007
`
`described in detail with reference to FIG. 5. As long as all
`daily tests are passed, the generator column can continue to
`be used for patient elutions. As understood by those skilled
`in the art, one of the daily tests is a measure of Rb yield.
`If it is determined in step 214 that one of the daily tests
`failed, it is further determined whether a reload of the
`generator column 10 is permitted (step 216). Reloading is
`permitted if the daily test failed due insufficient Rb yield
`only. If the daily test failed for some other reason the
`generators column 10 cannot be further used, and the Sr is
`optionally recovered (step 222) before the generator column
`is disposed of (step 224), as described above. If an Sr
`reload is permitted, it is determined in step 218 whether the
`number of Sr reloads of the generator column 10 has
`exceeded a predetermined reload limit. A generator column
`in accordance with the invention can, be loaded with Sr at
`least three times before any significant Sr breakthrough
`occurs. If it determined in step 218 that the reload limit has
`been reached, certain jurisdictions require that the generator
`column be flushed and the eluate tested for: trace metals;
`sterility; radionuclide purity; pyrogens; and pH. If it is
`determined in step 218 that the reload limit, has not been
`reached, the process branches back to step 206 and the
`generator column is reloaded with Sr and steps 208-218
`are repeated.
`0029 FIG. 5 is a flowchart illustrating principle steps
`involved in the daily use of the generator column 10 in
`accordance with the invention. Prior to each days use of the
`generator column 10, the generator column 10 is flushed
`with 50 ml of sterile saline solution (step 300) in order, to
`remove any strontium breakthrough from the generator
`column 10 into the waste vessel 90. The operator then waits
`for a predetermined period of time (step 302) before per
`forming a calibration elution (step 304). As is well under
`stood by those skilled in the art, under stable conditions the
`generator column maintains a SrfRb equilibrium which
`is achieved after about 10 minutes. Consequently, the pre
`determined wait before a calibration elution is performed is
`at least 10 minutes. After the required wait, the generator
`column is eluted with about 15 ml of sterile saline solution
`at a constant flow rate of about 15 ml/minute. The calibration
`eluate is tested (step 306) for Rb yield and Sr break
`through. In step 308 it is determined whether the yield is
`above a predetermined radioactivity limit. As is understood
`by those skilled in the art, the half life of Rb is very short
`(i.e. 76 seconds). Consequently, in one embodiment the Rb
`yield is measured using a positron counter during the
`elution, in a manner well known in, the art.
`0030) In step 310, it is determined whether the Sr, Sr
`breakthrough is less than a predetermined breakthrough
`limit. As is also understood by those skilled in the art, all
`jurisdictions define a threshold for permissible levels of Sr,
`Sr breakthrough. As is further understood by those skilled
`in the art, the strontium breakthrough is readily determined
`by testing the radioactivity of the elution after about 26
`minutes has elapsed, at which time the amount of residual
`Rb is insignificant and does not distort the test results.
`0031. Before daily use begins, a cumulative volume of all
`fluids flushed and eluted through the generator column 10 is
`computed. Since the generator column 10 in accordance
`with the invention is repeatedly reloaded with Sr, each
`generator column is identified by a unique identifier, in one
`embodiment a serial number. If the user of a generator
`
`column 10 does not have the facility to reload the generator
`column 10, the user must return the generator column 10 to
`the manufacturer, along with a cumulative total of fluid
`flushed and eluted through the column during that use.
`Likewise, when a reloaded column is Supplied to a user, a
`cumulative volume of fluid used to flush and elute the
`column during all prior reload(s) and use(s) is provided to
`the user. Control software used to control a volume of fluid
`used during generator column 10 flushes and elutions
`accepts the cumulative Volume and stores it. The control
`software then recomputes the cumulative volume after each
`subsequent flush or elution of the generator column 10. That
`computed cumulative Volume is compared (step 312) to a
`predefined volume limit. In accordance with one embodi
`ment of the invention, empirical data has shown that 10 to
`30 litres of sterile saline solution 100 can be pumped through
`the generator column 10 before significant Sr break
`through is experienced, so the Volume limit may be set
`between 10 and 30 litres.
`0032) If each of the tests 308-312 is successfully passed,
`patient elutions (step 314) may be performed in a manner
`well known in the art. After each elution, it is necessary to
`wait a predetermined period of time, about 5 to 10 minutes,
`(step 316) to permit Rb to regenerate. After each elution,
`the cumulative Volume is recomputed by adding to the
`cumulative volume a volume of fluid pumped through the
`generator column 10 during the patient elution. Then it, is
`determined whether the control system date has, changed,
`i.e. a new day has begun (step 318). If not, the cumulative
`volume is compared to the predetermined volume limit. If
`the Volume limit has been exceeded, the generator column is
`disposed of (step 324).
`0033) If it is determined in step 318 that the control
`system date has changed, the generator column 10 must be
`flushed and re-tested per steps 300-312, as described above.
`If those tests determine that the Rb yield is less than a
`predetermined limit (step 308) then it is determined in step
`320 whether the reload limit has been exceeded and if not
`the generator column 10 is returned for reload and pre-use
`testing (step 322). Otherwise, the generator column is dis
`posed of (step 324). It should be noted that if any of tests
`308-312 fail, the generator column 10 may be returned to the
`manufacturer who determines whether the generator column
`10 can be reloaded (step 320) and disposes of the generator
`column 10 (step 324) if it cannot be reloaded.
`0034. The generator column 10 in accordance with the
`invention reduces the expense of cardiac perfusion imaging
`while ensuring compatibility with 3D PET imaging systems
`by enabling low pressure, low flow rate elutions that can be
`precisely flow controlled. Research has conclusively estab
`lished that the generator column 10 in accordance with the
`invention remains sterile and pyrogen-free for a period of at
`least six months when used in accordance with the proce
`dures and limits described above.
`0035 Although the invention has been explained with
`reference to 3D PET imaging systems, it should be under
`stood that the generator column 10 is equally compatible
`with 2D PET imaging systems and provides the same
`advantages of low cost, precise flow control, low pressure
`and low flow elution and a long service life.
`0036) The embodiment(s) of the invention described
`above is(are) intended to be exemplary only. The scope of
`
`

`

`US 2007/O 140958 A1
`
`Jun. 21, 2007
`
`the invention is therefore intended to be limited solely by the
`Scope of the appended claims.
`I claim:
`1. A method of preparing a SrfRb generator column
`for low pressure elution, comprising:
`filling the generator column with an ion exchange mate
`rial that tightly binds Sr but not Rb, and compacting
`the ion exchange material to a density that permits at
`least 5 ml/min of fluid solution to be pumped through
`the generator column at a fluid pressure of 1.5 pounds
`per square inch (10 kPa):
`conditioning the ion exchange material; and
`loading the generator column with a solution of Sr.
`2. The method as claimed in claim 1 wherein compacting
`the ion exchange material comprises compacting the ion
`exchange material to a density of not more than 3 g/cm.
`3. The method as claimed in claim 2 wherein compacting
`the ion exchange material comprises repeatedly striking the
`generator column with a controlled force.
`4. The method as claimed in claim 2 wherein repeatedly
`striking the generator column comprises repeatedly deliver
`ing a controlled force that transfers about 0.1 Joule to the
`generator column.
`5. The method as claimed in claim 3 further comprising
`repeatedly striking the generator column to deliver the
`controlled force between 50 and 100 times in order to
`compact the ion exchange material.
`6. The method as claimed in claim 1 wherein conditioning
`the ion exchange material comprises eluting the material
`with a source of Sodium ions and Subsequently flushing the
`column with a sterile Saline solution.
`7. The method as claimed in claim 6 further comprising
`measuring a pH of the sterile saline solution after the
`generator column has been eluted with the source of sodium
`ions.
`8. The method as claimed in claim 1 further comprising
`eluting the generator column with a predetermined volume
`of sterile Saline Solution and testing the eluate to: determine
`whether the eluate is free of trace metals; determine whether
`the eluate is free of radionuclide impurities; measure a pH of
`the eluate; determine whether the eluate is sterile; and
`determine whether the eluate is free of pyrogens.
`9. The method as claimed in claim 1 further comprising
`reloading the generator column with Sr after the Sr has
`depleted to an extent that an elution of the generator column
`with the saline solution yields an Rb activity that is below
`a predetermined limit, until a total number of reloads reaches
`a predetermined radioactivity limit.
`10. The method as claimed in claim 1 further comprising,
`on a daily basis, flushing the generator column with a
`predetermined volume of sterile saline solution to remove
`any Sr or Sr breakthrough.
`
`11. The method as claimed in claim 10 further comprising
`waiting a predetermined period of time after the flushing,
`and eluting the generator column with a predetermined
`volume of sterile saline solution at a constant flow rate to
`obtain a calibration eluate offRb activity.
`12. The method as claimed in claim 11 further comprising
`measuring a total Rb activity of the calibration eluate
`during the elution for activity calibration.
`13. The method as claimed in claim 11 further comprising
`measuring a radiation activity level of the calibration eluate
`after a predetermined period of time has elapsed to deter
`mine whether a concentration of Sr or Sr in the test
`eluate is below a predetermined breakthrough limit.
`14. The method as claimed in claim 11 further compris
`ing:
`waiting a predetermined period of time after obtaining the
`calibration eluate, and eluting the generator column
`with a sterile saline solution to obtain a patient eluate
`of Rb activity; and
`computing for each generator column after each flush or
`elution, a cumulative volume of sterile saline flushed
`and eluted through the generator column, and disposing
`of the generator column when the cumulative Volume
`exceeds a predetermined Volume limit.
`15. An SrfRb generator column, comprising:
`a fluid impervious cylindrical container having a cover for
`closing the container in a fluid tight seal, and further
`having an inlet for connection of a conduit for deliv
`ering a fluid into the container and an outlet for
`connection of a conduit for conducting the fluid from
`the container, and
`an ion exchange material filling the container, the ion
`exchange material being compacted within the con
`tainer to a density that permits the ion exchange mate
`rial to be eluted at a flow rate of at least 5 ml/min at
`fluid pressure of 1.5 pounds per square inch (10 kPa).
`16. The SrfRb generator column as claimed in claim
`15 wherein the ion exchange material comprises C-hydrous
`tin dioxide.
`17. The SrfRb generator column as claimed in claim
`16 wherein a total volume of the C-hydrous tin dioxide in the
`generator column is about 1.5 cm.
`18. The SrfRb generator column as claimed in claim
`17 wherein the C-hydrous tin dioxide has a density of about
`3 g/cm.
`19. The SrfRb generator column as claimed in claim
`15 further comprising a particle filter at e