US009814826B2
`
`(12) United States Patent
`US 9,814,826 B2
`(10) Patent No.:
`Hidem et al.
`(45) Date of Patent:
`*Nov. 14, 2017
`
`(54)
`
`INTEGRATED STRONTIUM-RUBIDIUM
`RADIOISOTOPE INFUSION SYSTEMS
`
`(71) Applicant: Bracco Diagnostics Inc., Monroe
`Township, NJ (US)
`
`(72)
`
`Inventors: Stephen E. Hidem, Edina, MN (US);
`Aaron M. Fontaine, Minneapolis, MN
`(US); Janet L. Gelbach, Schaumburg,
`IL (US); Patrick M. McDonald,
`Omaha, NE (US); Kathryn M. Hunter,
`Knoxville, TN (US); Rolf E. Swenson,
`Silver Spring, MD (US); Julius P.
`Zodda, Mercerville, NJ (US)
`
`(58) Field of Classification Search
`CPC .. A61M 5/007; A61M 5/1001; A61M 5/1002;
`A61M 5/ 1007;
`
`(Continued)
`
`(56)
`
`References Cited
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`
`3,483,867 A
`3,535,085 A
`
`12/ l 969 Markovitz
`10/ l 970 Shumate
`
`(Continued)
`
`FOREIGN PATENT DOCUMENTS
`
`(73) Assignee: Bracco Diagnostics Inc., Monroe
`Township, NJ (US)
`
`CA
`CN
`
`( * ) Notice:
`
`Subject to any disclaimer, the term of this
`patent is extended or adjusted under 35
`U.S.C. 154(b) by 0 days.
`
`This patent is subject to a terminal dis-
`claimer.
`
`(21) Appl. No.: 15/620,320
`
`(22)
`
`Filed:
`
`Jun. 12, 2017
`
`(65)
`
`Prior Publication Data
`
`US 2017/0274138 A1
`
`Sep. 28, 2017
`
`Related U.S. Application Data
`
`(63) Continuation of application No. 15/389,200, filed on
`Dec. 22, 2016, now Pat. No. 9,750,869, which is a
`(Continued)
`
`(51)
`
`Int. Cl.
`A6IM 5/00
`A6IM 5/14
`
`(2006.01)
`(2006.01)
`(Continued)
`
`(52) U.S. Cl.
`CPC ............. A6IM 5/007 (2013.01); A6IB 6/037
`(2013.01); A6IB 6/107 (2013.01); A6IB 6/481
`(2013.01);
`
`2913373 Al
`1968653 A
`
`4/2008
`5/2007
`
`(Continued)
`
`OTHER PUBLICATIONS
`
`Alvarez-Diez et a1. “Manufacture of strontium-82/rubidium-82 gen-
`erators and quality control of rubidium-82 chloride for myocardial
`perfusion imaging in patients using positron emission tomography,”
`Applied Radiation and Isotopes, 1999, pp. 1015 -1023 .
`(Continued)
`
`Primary Examiner 7 Charles A Marmor, II
`Assistant Examiner 7 Carrie R Dorna
`
`(74) Attorney, Agent, or Firm 7 Fredrikson & Byron,
`PA.
`
`(57)
`
`ABSTRACT
`
`Methods for setting up, maintaining and operating a radio-
`pharmaceutical infusion system, that includes a radioisotope
`generator, are facilitated by a computer of the system. The
`computer may include pre-programmed instructions and a
`computer interface, for interaction with a user of the system,
`for example, in order to track contained volumes of eluant
`and/or eluate, and/or to track time from completion of an
`elution performed by the system, and/or to calculate one or
`more system and/or injection parameters for quality control,
`and/or to perform purges of the system, and/or to facilitate
`diagnostic imaging.
`
`(Continued)
`
`30 Claims, 27 Drawing Sheets
`
`
`
`JUBILANT EXHIBIT 1036
`
`Jubilant v. Bracco, |PR2018-01449
`
`JUBILANT EXHIBIT 1036
`Jubilant v. Bracco, IPR2018-01449
`
`

`

`US 9,814,826 B2
`
`Page 2
`
`Related US. Application Data
`
`(56)
`
`continuation of application No. 12/808,467, filed as
`application No. PCT/US2009/047031 on Jun. 11,
`2009, now Pat. No. 9,607,722, which is a continu-
`ation of application No. 12/137,377, filed on Jun. 11,
`2008, now Pat. No. 8,708,352, and a continuation of
`application No. 12/137,363, filed on Jun. 11, 2008,
`now Pat. No. 7,862,534, and a continuation of appli-
`cation No. 12/137,356, filed on Jun. 11, 2008, now
`Pat. No. 8,317,674, and a continuation of application
`No. 12/137,364, filed on Jun. 11, 2008, now Pat. No.
`9,597,053.
`
`(51)
`
`Int. Cl.
`A613 90/00
`A61M 5/145
`G21F 3/00
`A61M 5/158
`G21F 7/00
`A61M 5/168
`G21G 1/00
`A613 6/00
`A613 6/03
`G21G 4/08
`A613 50/13
`A61M 5/142
`A61K 51/00
`G06F 21/31
`A613 6/10
`A613 50/10
`A61N 5/10
`3623 3/00
`
`(2016.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2006.01)
`(2016.01)
`(2006.01)
`(2006.01)
`(2013.01)
`(2006.01)
`(2016.01)
`(2006.01)
`(2006.01)
`
`(52) us. Cl.
`CPC .............. A613 6/507 (2013.01); A613 50/13
`(2016.02); A613 90/39 (2016.02); A61K 51/00
`(2013.01); A61M 5/14 (2013.01); A61M 5/142
`(2013.01); A61M 5/1409 (2013.01); A61M
`5/1452 (2013.01); A61M 5/158 (2013.01);
`A61M 5/16854 (2013.01); A61M 5/16881
`(2013.01); A61N 5/1001 (2013.01); A61N
`5/1007 (2013.01); A61N 5/1075 (2013.01);
`G06F 21/31 (2013.01); G21F 3/00 (2013.01);
`G21F 7/00 (2013.01); G21G 1/001 (2013.01);
`G21G 1/0005 (2013.01); G21G 4/08
`(2013.01); A613 2050/105 (2016.02); A613
`2090/392 (2016.02); A61M 2005/1403
`(2013.01); A61M 2205/18 (2013.01); A61M
`2205/276 (2013.01); A61M 2205/50 (2013.01);
`A61M 2205/505 (2013.01); A61M 2205/52
`(2013.01); A61M 2209/084 (2013.01); A61N
`2005/1021 (2013.01); A61N 2005/1022
`(2013.01); A61N 2005/1074 (2013.01); A61N
`2005/1094 (2013.01); B62B 3/005 (2013.01);
`G21G 2001/0031 (2013.01)
`
`(58) Field of Classification Search
`CPC A61M 5/101475/1017; A61M 5/1027; A61M
`5/1028; A61M 5/1071; A61M 5/14;
`A61M 5/142; A61M 2005/1021; G21G
`4/08; G21G 1/0005; G06F 19/3468;
`A61B 2050/105
`
`See application file for complete search history.
`
`References Cited
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`
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`Carleton Institute for Electrical and Computer Engineering School
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`R. Klein, “Precision control of eluted Activity from a Sr/Rb gen-
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`Francisco, CA, USA, Sep. 1-5, 2004, 4 pages.
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`in Point-of-Care Testing,”
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`Oct. 2001, pp. 1307-1315.
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`“Medfusion 3000 Series Technical Service Manual,” Smiths Medi-
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`“BodyGuard 323 Infusion Pump System Operator Manual,”
`Caesarea Medical Electronics Ltd, Mar. 2009, 81 pages.
`“Alaris GH Syringe Pump Directions for Use,” Cardinal Health,
`Oct. 2005, 34 pages.
`“Auto Syringe AS40A: Model AS40A Infusion Pump Operation
`Manual,” Baxter, Aug. 1993, 84 pages.
`“CardioGen-82 Rubidium Rb 82 Generator for Elution of Rubidium
`Chloride Rb 82 Injection,” Bracco Diagnostics, May 2000, 13
`pages.
`
`

`

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`NOV. 14, 2017
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`U.S. Patent
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`NOV. 14, 2017
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`U.S. Patent
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`Nov. 14, 2017
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`U.S. Patent
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`Nov. 14, 2017
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`Sheet 27 of 27
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`US 9,814,826 B2
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`1
`INTEGRATED STRONTIUM-RUBIDIUM
`RADIOISOTOPE INFUSION SYSTEMS
`
`CROSS REFERENCE TO RELATED
`APPLICATIONS
`
`This application is a continuation of US. patent applica-
`tion Ser. No. 15/389,200, filed Dec. 22, 2016, which is a
`continuation of US. patent application Ser. No. 12/808,467,
`filed Jun. 16, 2010, now US. Pat. No. 9,607,722, issued
`Mar. 28, 2017, which is a 371 National Stage of Intema-
`tional Application No. PCT/USO9/47031,
`filed Jun. 11,
`2009, which in turn is a continuation of the following four
`patent applications: US. patent application Ser. No. 12/ 137,
`356, filed Jun. 11, 2008, now US. Pat. No. 8,317,674, issued
`Nov. 27, 2012; US. patent application Ser. No. 12/137,363,
`filed Jun. 11, 2008, now US. Pat. No. 7,862,534, issued Jan.
`4, 2011; US. patent application Ser. No. 12/137,364, filed
`Jun. 11, 2008, now US. Pat. No. 9,597,053, issued Mar. 21,
`2017; and US. patent application Ser. No. 12/137,377, filed
`Jun. 11, 2008, now US. Pat. No. 8,708,352, issued Apr. 29,
`2014. The entire contents of all of these applications are
`incorporated herein by reference.
`
`TECHNICAL FIELD
`
`The present invention pertains to systems that generate
`and infuse radiopharmaceuticals, and, more particularly, to
`systems including computer-facilitated maintenance and/or
`operation.
`
`BACKGROUND
`
`for
`radioactive material
`Nuclear medicine employs
`therapy and diagnostic imaging. Positron emission tomog-
`raphy (PET)
`is one type of diagnostic imaging, which
`utilizes doses of radiopharmaceuticals, for example, gener-
`ated by elution within a radioisotope generator, that are
`injected, or infused into a patient. The infused dose of
`radiopharmaceutical is absorbed by cells of a target organ, of
`the patient, and emits radiation, which is detected by a PET
`scanner, in order to generate an image of the organ. An
`example of a radioactive isotope, which may be used for
`PET, is Rubidium-82 (produced by the decay of Strontium-
`82); and an example of a radioisotope generator, which
`yields a saline solution of Rubidium-82, via elution, is the
`CardioGen—82® available from Bracco Diagnostics Inc.
`(Princeton, N.J.). A PET scanner in combination with
`infused doses of
`radiopharmaceuticals may also be
`employed to quantify blood flow rate, for example, through
`the coronary arteries of a patient.
`Set up, maintenance and operational procedures for infu-
`sion systems that both generate and inject doses of radiop-
`harmaceuticals are relatively involved in order to assure the
`safety and efficacy of each injected dose for the patient.
`Efficiency in carrying out these procedures is highly desir-
`able for technical personnel, who work with these systems
`on a routine basis and would like to avoid unnecessarily
`prolonged exposure to radioactive radiation. Thus there is a
`need for new system configurations that facilitate more
`efficient set up, maintenance and operation.
`
`BRIEF DESCRIPTION OF THE DRAWINGS
`
`The following drawings are illustrative of particular
`embodiments of the present invention and therefore do not
`limit the scope of the invention. The drawings are not to
`
`10
`
`15
`
`20
`
`25
`
`30
`
`35
`
`40
`
`45
`
`50
`
`55
`
`60
`
`65
`
`2
`
`scale (unless so stated) and are intended for use in conjunc-
`tion with the explanations in the following detailed descrip-
`tion. Embodiments of the present invention will hereinafter
`be described in conjunction with the appended drawings,
`wherein like numerals denote like elements.
`
`FIG. 1A is a first perspective view of an infusion system,
`according to some embodiments of the present invention.
`FIG. 1B is another perspective view of a portion of a
`cabinet structure of the system shown in FIG. 1A, according
`to some embodiments.
`
`FIG. 1C is a second perspective view of the system shown
`in FIG. 1A, according to some embodiments.
`FIG. 1D is a schematic of an infusion circuit, according to
`some embodiments of the present invention.
`FIG. IE is a perspective view of exemplary sample vial
`shielding that may be employed in conjunction with the
`infusion system of FIG. 1A.
`FIG. 2A is a perspective view of a shielding assembly for
`an infusion system, such as that shown in FIGS. 1A-C,
`according to some embodiments of the present invention.
`FIG. 2B is a perspective view of a framework of the
`system, according to some embodiments, and FIG. 2B-1 is
`an enlarged detailed view of a component of the system,
`according to some embodiments.
`FIG. 3A is another perspective view of the shielding
`assembly shown in FIG. 2A.
`FIG. 3B is a perspective view of the infusion circuit,
`shown in FIG. 1C, configured and routed, according to some
`embodiments.
`
`FIG. 3C is a perspective view of a disposable infusion
`circuit subassembly, according to some embodiments.
`FIG. 3D is a frame for the subassembly shown in FIG. 3C,
`according to some embodiments.
`FIG. 4 is a main menu screen shot from an interface of a
`
`computer, which may be included in systems of the present
`invention, according to some embodiments.
`FIG. 5Ais a schematic showing a first group of successive
`screen shots from the computer interface, according to some
`embodiments.
`
`FIG. 5B is a pair of screen shots from the computer
`interface, which provide indications related to eluant volume
`levels in a reservoir of the system, according to some
`embodiments.
`
`FIG. 5C is a schematic showing a second group of
`successive screen shots from the computer interface, accord-
`ing to some embodiments.
`FIG. 6 is a schematic showing a third group of successive
`screen shots from the computer interface, according to some
`embodiments.
`
`FIGS. 7A-C are schematics showing a fourth group of
`successive screen shots from the computer interface, accord-
`ing to some embodiments.
`FIGS. 8A-B are schematics showing a fifth group of
`successive screen shots from the computer interface, accord-
`ing to some embodiments.
`FIGS. 9A-C are schematics showing a sixth group of
`successive screen shots from the computer interface, accord-
`ing to some embodiments.
`FIG. 10 is a schematic showing a seventh group of
`successive screen shots from the computer interface, accord-
`ing to some embodiments.
`FIG. 11 is an exemplary report which may be generated
`by the computer included in infusion systems, according to
`some embodiments.
`FIGS. 12A-B are schematics of alternative infusion cir-
`
`cuits that may be employed by embodiments of the present
`invention.
`
`

`

`US 9,814,826 B2
`
`3
`FIG. 12C is a schematic illustrating exemplary activity
`profiles of injected doses of a radiopharrnaceutical.
`
`DETAILED DESCRIPTION
`
`The following detailed description is exemplary in nature
`and is not
`intended to limit the scope, applicability, or
`configuration of the invention in any way. Rather,
`the
`following description provides practical
`illustrations for
`implementing exemplary embodiments. Utilizing the teach-
`ing provided herein, those skilled in the art will recognize
`that many of the examples have suitable alternatives that can
`be utilized.
`
`FIG. 1A is a first perspective view of an infusion system
`10, according to some embodiments of the present inven-
`tion, wherein system 10 is shown supported by a cabinet
`structure, which includes a platform 113 (seen better in FIG.
`2B) and a shell 13; shell 13 extends upward from a skirt 11,
`that surrounds platform 113, to surround an interior space in
`which a portion of infusion system 10 is contained (seen in
`FIG. 1C). Shell 13 may be formed from panels of injection-
`molded polyurethane fitted together according to methods
`known to those skilled in the art. FIG. 1A illustrates the
`
`cabinet structure of system 10 including a grip or handle 14,
`which extends laterally from shell 13, in proximity to an
`upper surface 131 thereof, and a post 142, which extends
`upward from shell 13, and to which a work surface, or tray
`16 and a computer 17 are, preferably, attached, via an
`ergonomic, positionable mount. According to some embodi-
`ments, computer 17 is coupled to a controller of system 10,
`which is mounted within the interior space surrounded by
`shell 13; and, a monitor 172 of computer 17 not only
`displays indications of system operation for a user of system
`10, but also serves as a device for user input (e.g. touch
`screen input). However, according to alternate embodi-
`ments, another type of user input device, known to those
`skilled in the art, may be employed by computer 17. Other
`types of user input devices may be included, for example, a
`keyboard, a series of control buttons or levers, a bar code
`reader (or other reader of encoded information), a scanner,
`a computer readable medium containing pertinent data, etc.
`The user input device may be mounted on the cabinet
`structure of system 10, as shown, or may be tethered thereto;
`alternatively the user input device may be remote from
`system 10, for example, located in a separate control room.
`According to some additional embodiments, another user
`input device, for example, in addition to a touch screen of
`computer 17, may be remote from system 10 and used to
`start and stop infusions, as well as to monitor system
`operation both during quality control infusions and during
`patient infusions. Operation of system 10, which is facili-
`tated by computer 17, will be described below, in conjunc-
`tion with FIGS. 4-9C.
`
`FIG. 1A further illustrates two pairs of wheels 121, 122,
`mounted to an underside of platform 113, to make system 10
`mobile; handle 14 is shown located at an elevation suitable
`for a person to grasp in order to maneuver system 10, from
`one location to another, upon pairs of wheels 121, 122.
`According to some preferred embodiments, one or both
`pairs of wheels 121, 122, are casters, allowing for rotation
`in a horizontal plane (swivel), in order to provide additional
`flexibility for maneuvering system 10 in relatively tight
`spaces.
`FIG. 1B is a perspective view of a portion of system 10,
`on a side 111 of the cabinet structure, which is in proximity
`to wheels 121, 122. FIG. 1B illustrates a lever or pedal 125,
`which is located for activation by a foot of the person, who
`
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`In a neutral
`grasps handle 14 to maneuver system 10.
`position, pedal 125 allows wheels 121, 122 to rotate, and, if
`embodied as casters, to swivel freely. Pedal 125 may be
`depressed to a first position which prevents a swiveling of
`wheels 121, 122, according to those embodiments in which
`wheels 121, 122 are casters, and may be further depressed to
`brake wheels 121, 122 from rolling and swiveling, upon
`reaching a desired location. According to some embodi-
`ments, braking may be designed to slow system 10, for
`example, when rolling down an incline, and, according to
`yet further embodiments, system 10 may include a motor to
`power movement thereof.
`FIG. 1B further illustrates: a rear access panel 174 of shell
`13, for example, providing access to circuit boards of the
`aforementioned controller contained within the interior
`
`space that is surrounded by shell 13; an optional lock 184,
`to secure panel 174; a power jack 118, for connecting system
`10 to a power source; and a printer 117 for providing
`documentation of each patient infusion carried out by sys-
`tem 10, and of system quality control test results. In some
`embodiments, system 10 may further include a power strip
`by which auxiliary equipment may be powered, and one or
`more additional electrical connectors, or ports (not shown),
`which are supported by platform 113 and may be integrated
`into shell 13, for example, in proximity to jack 118 or printer
`117; these electrical connectors/ports allow system 10 to
`communicate with, other devices used for nuclear i