(19) United States
`(12) Patent Application Publication (10) Pub. No.: US 2011/0178359 A1
`(43) Pub. Date:
`Jul. 21, 2011
`Hirschman et al.
`
`US 20110178359A1
`
`(54) SYSTEMIS FOR INTEGRATED
`RADIOPHARMACEUTICAL GENERATION,
`PREPARATION, TRANSPORTATION AND
`ADMINISTRATION
`
`(76) Inventors:
`
`PCT Fled:
`
`Appl. No.:
`
`(21)
`(22)
`(86). PCT No.:
`S371 (c)(1),
`(2), (4) Date:
`
`Alan D. Hirschman, Glenshaw, PA
`(US); Arthur E. Uber, III,
`Pittsburgh, PA (US); Kevin P.
`Cowan, Allison Park, PA (US);
`David M. Reilly, Pittsburgh, PA
`(US); Edward J. Rhinehart,
`Monroeville, PA (US); John
`Kalafut, Pittsburgh, PA (US);
`Bronwyn Uber, Pittsburgh, PA
`(US); Frederick W. Trombley, III,
`Gisbonia, PA (US); Steven J.
`Remis, Ford City, PA (US); Paul D.
`Levin, Pittsburgh, PA (US); Scott
`Griffith, Murrysville, PA (US);
`Douglas Descalzi, Pittsburgh, PA
`(US); Richard Dewit, Mount
`Lebanon, PA (US); David M.
`Griffiths, Pittsburgh, PA (US)
`
`12/595,165
`
`Dec. 28, 2007
`
`PCT/US07/89101
`
`Jan. 20, 2011
`
`Related U.S. Application Data
`(60) Provisional application No. 60/878.334, filed on Jan.
`1, 2007, provisional application No. 60/878,333, filed
`on Jan. 1, 2007, provisional application No. 60/910,
`810, filed on Apr. 9, 2007.
`
`Publication Classification
`
`(51) Int. Cl.
`(2006.01)
`A6M 36/06
`(52) U.S. Cl. ............................................................ 600/4
`
`ABSTRACT
`(57)
`An integrated radiopharmaceutical patient treatment system
`is disclosed including a patient Support platform with an
`associated patient stimulus apparatus, an imager proximate
`the patient Support platform, a radiopharmaceutical fluid
`delivery system for infusing a radiopharmaceutical fluid into
`a patient, a patient monitor to be associated with a patient, and
`an integrated system controller operably associated with the
`patient stimulus apparatus, imager, radiopharmaceutical fluid
`delivery system, and patient monitor to control and coordi
`nate their operations. Within the patient treatment system the
`radiopharmaceutical fluid delivery system may be included
`comprising a radionuclide Supply module, a radiopharmaceu
`tical processing module, a quality control module, a patient
`injection module, and a controller. Ahazardous fluid handling
`system including a docking station and a hazardous fluid
`transport device adapted to detachably dock with the docking
`station is further disclosed.
`
`CREATE ISOOPE
`
`10
`
`CREATE
`NJECTABLE DRUG
`
`20
`
`30
`
`4. O
`
`y
`
`DOSE PREPARATION
`
`PREPARE
`
`PATIENT
`
`DOSE DELIVERY
`
`DOSEU E. 7 O
`
`6 O
`
`PTAKE
`
`ACQUIRE IMAGE DATA
`OTHER MEASUREMENTS
`
`DATA RECONSTRUCTION
`& ANALYSS
`
`80
`
`Bracco 2001
`Jubilant v. Bracco
`IPR2018-01449
`
`1
`
`

`

`Patent Application Publication
`
`Jul. 21, 2011 Sheet 1 of 35
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`US 2011/0178359 A1
`
`
`
`
`
`CREATE ISOTOPE
`
`
`
`
`
`CREATE
`NJECTABLE DRUG
`
`
`
`DOSE PREPARATION
`
`PREPARE PATIENT
`
`10
`
`20
`
`30
`
`40
`
`
`
`50
`
`DOSE DELIVERY
`
`60
`
`70
`
`8O
`
`
`
`DOSE UPTAKE
`
`
`
`
`
`ACQUIRE IMAGE DATA
`OTHER MEASUREMENTS
`
`DATA RECONSTRUCTION
`8. ANALYSS
`
`FIG.1
`
`2
`
`

`

`Patent Application Publication
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`Jul. 21, 2011 Sheet 2 of 35
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`US 2011/0178359 A1
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`
`
`
`
`
`
`
`
`
`
`WEIS?S
`
`NETTO?IN00
`
`3
`
`

`

`Patent Application Publication
`
`Jul. 21, 2011 Sheet 3 of 35
`
`US 2011/0178359 A1
`
`
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`

`Patent Application Publication
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`Jul. 21, 2011 Sheet 4 of 35
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`US 2011/0178359 Al
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`5
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`

`Patent Application Publication
`
`Jul. 21, 2011 Sheet 5 of 35
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`US 2011/0178359 A1
`
`
`
`6
`
`

`

`Patent Application Publication
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`Jul. 21, 2011 Sheet 6 of 35
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`US 2011/0178359 A1
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`
`
`7
`
`

`

`Patent Application Publication
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`Jul. 21, 2011 Sheet 7 of 35
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`US 2011/0178359 A1
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`
`
`8
`
`

`

`Patent Application Publication
`
`Jul. 21, 2011 Sheet 8 of 35
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`US 2011/0178359 A1
`
`
`
`FIG.4B
`
`9
`
`

`

`Patent Application Publication
`
`Jul. 21, 2011 Sheet 9 of 35
`
`US 2011/0178359 A1
`
`
`
`s
`
`10
`
`

`

`Patent Application Publication
`
`Jul. 21, 2011 Sheet 10 of 35
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`US 2011/0178359 A1
`
`
`
`s
`
`11
`
`

`

`Patent Application Publication
`
`Jul. 21, 2011 Sheet 11 of 35
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`US 2011/0178359 A1
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`

`

`Patent Application Publication
`
`Jul. 21, 2011 Sheet 12 of 35
`
`US 2011/0178359 A1
`
`901
`
`900a -
`
`902
`
`901
`
`900b -
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`902
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`13
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`

`

`Patent Application Publication
`
`Jul. 21, 2011 Sheet 13 of 35
`
`US 2011/0178359 A1
`
`
`
`:
`
`E.
`
`:
`
`14
`
`

`

`Patent Application Publication
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`Jul. 21, 2011 Sheet 14 of 35
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`US 2011/0178359 A1
`
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`15
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`

`

`Patent Application Publication
`
`Jul. 21, 2011 Sheet 15 of 35
`
`US 2011/0178359 A1
`
`1004
`
`( SHE DED CONANER
`ORUC
`CONTAINER
`
`
`
`DEVICE &
`O DRUC DATA
`
`1028
`
`DOSMETER
`CONTROL
`
`1023 1. 1002
`
`1024
`
`1026
`1022
`
`FIG.14B
`
`16
`
`

`

`Patent Application Publication
`
`Jul. 21, 2011 Sheet 16 of 35
`
`US 2011/0178359 A1
`
`
`
`
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`
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`Oy L’914
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`TO?IN00 WEIS?S |[] WHIS?S|
`
`17
`
`

`

`Patent Application Publication
`
`Jul. 21, 2011 Sheet 17 of 35
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`US 2011/0178359 A1
`
`
`
`18
`
`

`

`Patent Application Publication
`
`Jul. 21, 2011 Sheet 18 of 35
`
`US 2011/0178359 A1
`
`SHIELDE)
`CONANER
`
`ISOTOPE
`GENERATOR
`
`GEN
`CONTR
`OL
`
`GENERATOR
`E
`U
`
`
`
`1004'
`DRUG DATA
`
`PATIENT DATA
`PRESCRIPTION
`
`
`
`DOSMETER
`CONTROL
`
`------------
`
`t-----------
`
`FIG.16
`
`19
`
`

`

`Patent Application Publication
`
`Jul. 21, 2011 Sheet 19 of 35
`
`US 2011/0178359 A1
`
`1 OO6O
`
`1008a
`
`1058 1056
`
`002
`
`
`
`
`
`ISOTOPE
`GENERATOR
`
`CHEMESTRY
`UNIT
`
`
`
`20
`
`

`

`Patent Application Publication
`
`Jul. 21, 2011 Sheet 20 of 35
`
`US 2011/0178359 A1
`
`1002c(R)
`1058c
`1023c
`1056c(R) - O
`
`1024c(R)
`1048c(R)
`
`
`
`
`
`
`
`
`
`
`
`
`
`1048c(L)
`
`1050c(L)
`1055c(L)
`
`
`
`1052c(L)
`
`21
`
`

`

`Patent Application Publication
`
`Jul. 21, 2011 Sheet 21 of 35
`
`US 2011/0178359 A1
`
`SALINE FLUSH IN
`
`/
`
`
`
`N
`
`OUT TO PATIENT
`
`1048c(L),
`LEFT SYRINGE
`MULTIPATIENT
`
`1048c(R),
`RIGHT SYRINGE
`SINGLE PATIENT
`
`FIG.21
`
`
`
`FIG.22A
`
`22
`
`

`

`Patent Application Publication
`
`Jul. 21, 2011 Sheet 22 of 35
`
`US 2011/0178359 A1
`
`
`
`1023d'
`
`-1002d
`
`108Od'
`
`FIG.22B
`
`23
`
`

`

`Patent Application Publication
`
`Jul. 21, 2011 Sheet 23 of 35
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`US 2011/0178359 A1
`
`
`
`24
`
`

`

`Patent Application Publication
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`Jul. 21, 2011 Sheet 24 of 35
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`US 2011/0178359 A1
`
`
`
`
`
`
`
`1204
`
`1204
`
`12O6
`
`FIG.26
`
`25
`
`

`

`Patent Application Publication
`
`Jul. 21, 2011 Sheet 25 of 35
`
`US 2011/0178359 A1
`
`
`
`FIG.27
`
`804
`
`810b
`
`
`
`820
`
`26
`
`

`

`Patent Application Publication
`
`Jul. 21, 2011
`
`Sheet 26 Of 35
`
`US 2011/0178359 A1
`
`
`
`850
`
`851
`856
`
`853
`
`
`
`CO CN LO
`
`
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`853
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`854
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`FIG.31
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`mae
`mae
`~ Ø
`ØØ4)
`Ø Ø
`
`N :::::::
`
`854
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`FIG.52
`
`27
`
`

`

`Patent Application Publication
`
`Jul. 21, 2011 Sheet 27 of 35
`
`US 2011/0178359 A1
`
`850
`
`8510
`
`851 a 1 85OO
`
`852O
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`761
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`T s
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`
`FIG.35A 7'
`
`28
`
`

`

`Patent Application Publication
`
`Jul. 21, 2011 Sheet 28 of 35
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`US 2011/0178359 A1
`
`
`
`FIG.35B
`
`29
`
`

`

`Patent Application Publication
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`Jul. 21, 2011 Sheet 29 of 35
`
`US 2011/0178359 A1
`
`
`
`FIG.35C
`
`30
`
`

`

`Patent Application Publication
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`Jul. 21, 2011 Sheet 30 of 35
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`US 2011/0178359 A1
`
`
`
`FIG.36A
`
`31
`
`

`

`Patent Application Publication
`
`Jul. 21, 2011 Sheet 31 of 35
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`US 2011/0178359 A1
`
`
`
`FIG.36B
`
`32
`
`

`

`Patent Application Publication
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`Jul. 21, 2011 Sheet 32 of 35
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`US 2011/0178359 A1
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`
`
`FIG.38
`
`33
`
`

`

`Patent Application Publication
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`Jul. 21, 2011 Sheet 33 of 35
`
`US 2011/0178359 A1
`
`
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`

`

`Patent Application Publication
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`Jul. 21, 2011 Sheet 34 of 35
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`US 2011/0178359 A1
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`
`
`869,
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`

`Patent Application Publication
`
`Jul. 21, 2011 Sheet 35 of 35
`
`US 2011/0178359 A1
`
`
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`

`

`US 2011/0178359 A1
`
`Jul. 21, 2011
`
`SYSTEMIS FOR INTEGRATED
`RADIOPHARMACEUTICAL GENERATION,
`PREPARATION, TRANSPORTATION AND
`ADMINISTRATION
`
`RELATED APPLICATIONS
`0001. This application claims the benefit of U.S. Provi
`sional Patent Application No. 60/910,810 entitled “Methods
`and Systems for Integrated Radiopharmaceutical Generation,
`Preparation, and Administration filed Apr. 9, 2007 and, fur
`ther, claims the benefit of U.S. Provisional Patent Application
`No. 60/878,334 entitled “Methods and Equipment for Han
`dling Radiopharmaceuticals' and U.S. Provisional Patent
`Application No. 60/878.333 entitled “Pharmaceutical Dosing
`Method’, both filed Jan. 1, 2007.
`
`BACKGROUND OF THE INVENTION
`0002 1. Field of the Invention
`0003. The invention disclosed herein relates to generation,
`preparation, and administration of pharmaceutical Sub
`stances, typically intrinsically harmful or toxic pharmaceuti
`cal Substances such as radioactive pharmaceutical Sub
`stances, generally known as radiopharmaceuticals to human
`and animal Subjects and, more specifically, to methods and
`systems and associated components for the generation,
`preparation, transportation, and administration of fluid
`radiopharmaceutical Substances to human and animal Sub
`jects. The non-radiation shielding aspects of the various
`embodiments presented herein are applicable to all medical
`fluid applications involving the preparation and delivery/ad
`ministration of Such non-radioactive medical fluids.
`0004 2. Description of Related Art
`0005 Administration of radioactive pharmaceutical sub
`stances or drugs, generally termed radiopharmaceuticals, is
`often used in the medical field to provide information or
`imagery of internal body structures and/or functions includ
`ing, but not limited to, bone, vasculature, organs and organ
`systems, and other tissue. Additionally, Such radiopharma
`ceuticals may be used as therapeutic agents to kill or inhibit
`the growth of targeted cells or tissue, such as cancer cells.
`However, radiopharmaceutical agents used in imaging pro
`cedures and therapeutic procedures typically include highly
`radioactive nuclides of short half-lives and are hazardous to
`attending medical personnel. These agents are toxic and can
`have physical and/or chemical effects for attending medical
`personnel Such as clinicians, imaging technicians, nurses, and
`pharmacists. Excessive radiation exposure is harmful to
`attending medical personnel due to their occupational
`repeated exposure to the radiopharmaceuticals. However, due
`to the short half-life of typical radiopharmaceutical agents
`and Small applied dosages, the radiation exposure risk to
`benefit ratio for individual patients is acceptable. The con
`stant and repeated exposure of medical personnel to radiop
`harmaceuticals over an extended period of time is a signifi
`cant problem in the nuclear medicine field.
`0006. A number of techniques are used in the medical field
`to reduce radiation exposure to attending medical personnel
`associated with the creation, handling, transport, dose prepa
`ration, and administration of radiopharmaceuticals to
`patients. These techniques encompass one or more of mini
`mizing the time of exposure of medical personnel, maintain
`ing distance between medical personnel and the Source of
`radiation, and/or shielding medical personnel from the Source
`
`of radiation. As a certain amount of close-proximity interfac
`ing between medical personnel and radiopharmaceutical
`agents (including patients who have or are to receive radiop
`harmaceutical agents) is somewhat inevitable during the cur
`rent practice of generating, preparing, and administering
`radiopharmaceutical agents to patients and caring for these
`patients, radiation shielding has considerable importance in
`the nuclear medicine field. A simple patient radiation guard is
`disclosed in U.S. Pat. No. 3,984,695 to Collica et al. as an
`example. It is well-known, for example, to use shielded con
`tainers known as "pigs' for general handling and transport of
`radiopharmaceutical containers (bottles, vials, etc.) and use
`shielded Syringes to remove the radiopharmaceutical from
`the radiopharmaceutical containers and administer the same
`to individual patients. Radiopharmaceutical transport pigs
`are also configured to transport Syringes. Examples of
`shielded transport pigs are disclosed in U.S. Pat. No. 5,274,
`239 to Lane et al. which is incorporated by reference and U.S.
`Pat. No. 6,425,174 to Reich, also incorporated herein by
`reference. An example of a shielded Syringe is disclosed in
`U.S. Pat. No. 4.307,713 to Gaskin et al. which is also incor
`porated herein by reference. Other shielded syringes are
`known from U.S. Pat. No. 6,589,158 to Winkler; United
`States Patent Application Publication No. 2004/0015038 to
`Lemer; and U.S. Pat. No. 6,162,198 to Coffey et al., all
`incorporated herein by reference.
`0007 As is generally known in the nuclear medicine field,
`radiation emanates in all directions from radioactive Sub
`stances and, consequently, emanates in all directions from an
`unshielded container holding a radioactive substance. While
`radiation may be scattered or deflected, this effect is generally
`Small enough that it is sufficient to protect personnel from the
`direct “shine' of radiation and not be too concerned with
`scattered radiation, unless the activity levels in the container
`are very high. Transport pigs come in various configurations
`for holding radiopharmaceutical containers (bottles, vials,
`Syringes, etc.). One form often includes a removable cover
`that allows access to the held radiopharmaceutical container,
`as disclosed in United States Patent Application Publication
`No. 2005/0107698 to Powers et al. incorporated herein by
`reference. Such containers may be in the form of avial with an
`elastomeric, for example, rubber, stopper, or septum which
`retains the radiopharmaceutical agent in the vial. When the
`pig cover is in place, the radiation exposure is acceptable.
`When the cover is opened or removed, a radiation “shine'
`emanates from the opening. A common sterile transfer pro
`cedure to remove the radiopharmaceutical agent from its con
`tainer is to pierce the elastomeric stopper or septum with a
`sterile needle on a Syringe. Commonly, the exposed surface of
`the stopper or septum is sterilized with an alcohol wipe prior
`to piercing the stopper or septum with the transfer needle on
`the Syringe.
`0008 Syringes, during loading and once loaded with
`radiopharmaceutical agents, are commonly handled via
`Syringe shields and shielded glove boxes or containers, but
`may also be transported in a suitably configured transport pig
`as noted previously. Syringe shields are commonly hollow
`cylindrical structures that accommodate the cylindrical body
`of the Syringe and are constructed of lead or tungsten with a
`lead glass window that allows the handler to view the syringe
`plunger and liquid Volume within the Syringe. Due to its
`cylindrical configuration, Syringe shields protect against
`radiation emissions in a generally radial direction along the
`length of the syringe body but the two open ends of the
`
`37
`
`

`

`US 2011/0178359 A1
`
`Jul. 21, 2011
`
`Syringe shield provide no protection to the handler as there is
`radiation “shine’emanating from the two ends of the Syringe
`shield. Devices are further known for drawing radiopharma
`ceutical agents into Syringes. For example, U.S. Pat. No.
`5,927.351 to Zhu et al. discloses a drawing station for han
`dling radiopharmaceuticals for use in Syringes, incorporated
`herein by reference. In radiopharmaceutical delivery applica
`tions, devices are known for remotely administering radioac
`tive Substances from Syringes to minimize radiation expo
`Sures to attending medical personnel as disclosed in U.S. Pat.
`No. 5,514,071 to Sielaff Jr. et al. or 3,718,138 to Alexandrov
`etal. An automated device for controlled administering radio
`active substances is disclosed in U.S. Pat. No. 5,472.403 to
`Cornacchia et al. and is incorporated herein by reference. A
`system approach to controlling injectors used to inject radio
`active material into a patient is disclosed in published German
`Document No. DE 10 2005 O1O152.
`0009. In addition to the difficulties introduced by the haz
`ardous nature of radiopharmaceuticals, the short half-lives of
`Such radiopharmaceuticals further complicate the adminis
`tration of a properdosage to a patient. The radioactivity levels
`of the radiopharmaceutical agents used as tracers in, for
`instance, single-photon emission computerized tomography
`(SPECT) and positron emission tomography (PET) imaging
`procedures are measured by medical personnel. Such as radio
`pharmacists or nuclear medicine technologists, to determine
`the radiation dose that will be administered to the individual
`during the course of a diagnostic procedure. The radiation
`dose received depends on a number of factors including the
`half-life of the radiopharmaceutical agent and the initial
`radioactivity level of the radiopharmaceutical agent at the
`time it is injected into the individual. One known solution is to
`measure or calibrate the initial radioactivity of the radiophar
`maceutical and time the injection so that a dose of the desired
`level of radioactivity is delivered (as calculated from the
`half-life of the radiopharmaceutical). Often, radiation levels
`are determined as part of the dispensing or container filling
`process as disclosed generally in United States Patent Appli
`cation Publication No. 2006/0151048 to Tochon-Ganguy et
`al. or measured by a stand-alone device adapted to receive the
`radiopharmaceutical container as disclosed in U.S. Pat. No.
`7,151,267 to Lemer or 7.105,846 to Eguchi. Radiation detec
`tors have also been placed upon syringe shields and in-line
`with the radiopharmaceutical delivery system. For example,
`U.S. Pat. No. 4,401,108 to Gallon et al. discloses a syringe
`shield for use during drawing, calibration, and injection of
`radiopharmaceuticals. This syringe shield includes a radia
`tion detector for detecting and calibrating the radioactive
`dosage of the radiopharmaceutical drawn into the Syringe. A
`similar arrangement to that disclosed by Galkin et al. but in
`connection with a transport pig is disclosed in Japanese Pub
`lication No. JP2005-283431, assigned to Sumitomo Heavy
`Industries. U.S. Pat. Nos. 4,562,829 and 4,585,009 to Bergner
`and Barker et al. respectively, and incorporated herein by
`reference disclose strontium-rubidium infusion systems and a
`dosimetry system for use therein. The infusion system
`includes a generator of the strontium-rubidium radiopharma
`ceutical in fluid connection with a syringe used to Supply
`pressurized saline. Saline pumped through the strontium
`rubidium generator exits the generator either to the patient or
`to waste collection. Tubing in line between the generator and
`the patient passes in front of a dosimetry probe to count the
`number of disintegrations that occur. As the geometric effi
`ciency (or calibration) of the detector, the flow rate through
`
`the tubing, and Volume of the tubing is known, it is possible to
`measure the total activity delivered to the patient (for
`example, in milliCuries). Likewise, radiation measurements
`have been made upon blood flowing through the patient. For
`example, U.S. Pat. No. 4,409,966 to Lambrecht et al. dis
`closes shunting of blood flow from a patient through a radia
`tion detector. A significant quantity of information about
`nuclear medicine imaging devices and procedures can be
`found in WO 2006/651531A2 and WO 2007/010534A2 from
`Spectrum Dynamics LLC., incorporated herein by reference.
`A portable fluid delivery unit is known from U.S. Pat. No.
`6,773,673 to Layfleld et al., incorporated herein by reference.
`0010. As noted above, examples of the use of radiophar
`maceutical agents in diagnostic imaging procedures include
`positron emission tomography (PET) and single-photon
`emission computerized tomography (SPECT) which are non
`invasive, three-dimensional imaging procedures that provide
`information regarding physiological and biochemical pro
`cesses in patients. In effect, the radiopharmaceutical agent
`acts as a tracer to interact with the targeted area. An initial step
`in producing PET images or SPECT images of for example,
`vasculature, organs and organ systems, and/or other targeted
`tissue is to inject the patient with a dose of the radiopharma
`ceutical agent. The radiopharmaceutical agent is absorbed on
`or by certain cells in the body structure of interest and con
`centrates in this area. As an example, fluorodeoxyglucose
`(FDG) is a slight modification to the normal molecule of
`glucose, the basic energy fuel of cells, which readily accepts
`a radionuclide as a replacement to one of the atoms of the
`molecule. The radiopharmaceutical “tracer emits a positron
`which creates photons that can be detected as the tissue is
`scanned at various angles and the photons pass through a
`detector array. A computer is used to reconstruct a three
`dimensional color tracer image of the selected tissue struc
`ture.
`0011. With the foregoing background in place, exemplary
`current practice of generating, preparing, and administration
`of radiopharmaceuticals will now be described. Typical
`radiopharmaceutical treatment practice in the United States
`includes having the radiopharmaceutical agent initially gen
`erated off-site from a treatment location, typically a hospital,
`by an outside nuclear medicine facility and then delivered to
`the treatment location for further preparation, for example,
`individual dosing and administration. The treatment location,
`for example, a hospital, orders specific radioactive substances
`to be ready at specific time for specific patients. These sub
`stances are prepared by the outside nuclear medicine facility
`and with sufficient radioactivity that they will have the
`desired radioactivity level at the targeted time. For example,
`the outside nuclear medicine provider may have a facility
`equipped with a cyclotron or radioisotope generator in, for
`example, a lead-shielded enclosure wherein the radiopharma
`ceutical agent, namely, a radioactive isotope is generated or
`created. Further refining or dose preparation steps, namely,
`placing the radioisotope in injectable form, may occur at the
`off-treatment site. Thus, the outside provider may provide a
`radiopharmaceutical Substance to the treatment site having a
`desired radioactivity level at the targeted time. Further “indi
`vidual dose preparation of the radiopharmaceutical agent
`may occur at the treatment site. Alternatively, the outside
`provider may provide a “finished' radiopharmaceutical agent
`ready for injection to a specified patient at a specified time so
`that treatment site personnel are only required to confirm that
`the correct radioactive dosage is present in the radiopharma
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`ceutical agent, for example, in a stand-alone radiation dosim
`etry device as described previously. During the forgoing pro
`cess, there is frequent close-proximity contact with
`radioactive materials by personnel and, as described previ
`ously, handling and transport shielding devices are needed for
`the protection of these personnel.
`0012 Transport pigs are commonly employed to transport
`the radiopharmaceutical agents, which are individual doses
`prepared for individual patients, to the treatment facility. At
`the treatment facility, data about each unit dose is entered into
`a facility computer either manually or through reading a bar
`code, floppy disk, or other similar data format, which may
`accompany or be on the transport pig or the radiopharmaceu
`tical agent container. When it is time to deliver a specified unit
`dose to a specified patient, treatment facility personnel must
`remove, for example, a syringe containing the radiopharma
`ceutical agent from the transport pig and confirm that the dose
`in the Syringe is within the range prescribed for that patient.
`Alternatively, the attending personnel must transfer the
`radiopharmaceutical agent to a shielded syringe as identified
`previously and confirm dosage. If the dose is too high, some
`is discarded into a shielded waste container. If the dose is too
`low, either a different Syringe is used and/or additional agent
`is loaded into the syringe if available. While it possible for the
`attending treatment site personnel to be involved with dosage
`preparation, typical United States practice is to have the
`radiopharmaceutical agent delivered to the treatment site
`which will have the desired radioactivity level at the targeted
`time. Manual manipulation of the radiopharmaceutical agent
`at the treatment site is limited at the treatment site due to this
`procedure. Nonetheless, various manual checks are required
`to confirm that a correct radiopharmaceutical dose is ready
`for injection into a specific patient. These manual checks
`include visual inspections and radioactivity measurements as
`noted above.
`0013 As an example of the foregoing, in PET imaging, an
`injectable radiopharmaceutical agent Such as, for instance,
`FDG (fluorodeoxyglucose) is fabricated in a cyclotron device
`at an outside nuclear medicine facility. Thereafter, the FDG is
`processed to be in a radiopharmaceutical form and is trans
`ferred in an individual dose container (i.e., vial, bottle,
`Syringe, etc.) and the container loaded into a transport pig to
`prevent unnecessary radiation exposure to personnel. Such as
`the radio-pharmacist, technician, and driver responsible for
`creation, handling, and transport of the FDG from the cyclo
`tron site to the PET imaging site. Since the half-life of FDG is
`short, approximately 110 minutes, it is necessary to quickly
`transport the FDG to the PET imaging site. Depending upon
`the elapsed transport time and the initial radioactivity level of
`the FDG at the time of fabrication, the radioactivity level of
`the FDG may need to be re-measured at the PET imaging site.
`As an example, if the radioactivity level is too high, the
`transport radio-pharmacist of a radio-pharmacist at the PET
`imaging site may be required to dilute the FDG with a diluent
`Such as, for instance, saline solution, and remove part of the
`volume or extract fluid to reduce radioactivity prior to patient
`injection. During this entire process, the handling of FDG
`from creation to patient injection may be entirely manual.
`Within this process, shielding products, as described previ
`ously (i.e., transport pigs, Syringe shields, L-blocks, etc.) are
`used to shield individuals from FDG. While shielding may
`reduce the radiation exposure of the radio-pharmacist, the
`radio-pharmacist may still be exposed to emissions from the
`radiopharmaceutical agent during the manual mixing, Vol
`
`ume reduction, and/or dilution process needed to obtain the
`required dose. After injection and often after an additional
`delay to allow the radiopharmaceutical to reach and be
`absorbed by the desired regions of interest in the body, the
`patient is typically placed on a moveable bed that slides by
`remote control into a circular opening of an imaging scanner
`referred to as the gantry. Positioned around the circular open
`ing and inside the gantry are several rings of radiation detec
`tors. In one type of radiation detector, each detector emits a
`brief pulse of light every time it is struck with a gamma ray
`coming from the radionuclide within the patient's body. The
`pulse of light is amplified by a photomultiplier converted to an
`electronic signal and the information is sent to the computer
`that controls the apparatus and records imaging data.
`0014 For the sake of completeness, it should be noted that
`in the United States it also known to have radiopharmaceuti
`cal agents delivered in a multi-dose format to the treatment
`site. As a result, this multi-dose format must be divided into
`singular doses for individual patients at the treatment site.
`While it possible that this dividing may occur at the point of
`injection or administration, it more typical for a radio-phar
`macist or nuclear medicine technologist to perform the divid
`ing process in a “hot lab’ at the treatment facility. Individual
`radiopharmaceutical doses are then transported to the admin
`istration location within the treatment facility where the doses
`are administered to specific patients.
`0015. In Europe, radiopharmaceutical creation and dose
`preparation practice differs from United States practice in that
`these actions typically all occur within a “hot lab’ in the
`treatment facility again, typically, a hospital. As an example,
`the hospital itself typically has cyclotron or isotope genera
`tors (such as technetium generators manufactured by
`Mallinckrodt Inc., St. Louis, Mo.; Amersham Healthcare,
`2636 South Clearbrook Drive, Arlington Heights, Ill. 60005;
`or GE Healthcare Limited, Amersham Place, Little Chalfont,
`Buckinghamshire, United Kingdom) in a shielded location in
`the hot lab. Two manufactures of shielded glove boxes are
`Comecer in Italy and Lemer Pax in France. Hospital person
`nel create or extract the radioactive isotope, perform addi
`tional chemistry steps necessary to formulate the radioactive
`drug (i.e., radiopharmaceutical) early in the day, and then
`prepare unit doses for individual patients, generally close to
`the time the patient is to be injected with the radiopharma
`ceutical. While an internal “hot lab' has advantages in mini
`mizing hazardous material transport and improving internal
`information transfer, additional time and radiation burdens
`are placed on hospital staff as the measurement of radioac
`tivity levels at the various steps still depends upon manual
`insertion of a container (i.e., a vial, bottle, or syringe) into a
`dose calibrator and then repeated adjustments of the radioac
`tivity until the desired level is achieved. The unit dose radia
`tion level is commonly recorded manually or by a printer.
`0016. Within the prior art, systems for delivering hazard
`ous fluids are known as disclosed, for example, in U.S. Pat.
`No. 6,767,319 to Reilly et al. and United States Patent Appli
`cation Publication No. 2004/0254525 to Uber, III et al., the
`disclosures of which are incorporated herein by reference.
`Another system adapted to inject a radioactive liquid into a
`patient is disclosed in Japanese Publication No. W2000
`350783 (see also United States Patent Application Publica
`tion No. 2005/0085682 to Sasaki et al.), assigned to Sumi
`tomo Heavy Industries. This published patent application
`discloses a system which dispenses a volume of radioactive
`fluid into a coiled “medicine container” situated in a radiation
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`measuring unit. When the prescribed radiation dose is accu
`mulated in the coiled container, another syringe pushes saline
`through the coiled container and into a patient. A similar
`device and method is disclosed in Japanese Publication No.
`JP2002-306609, also assigned to Sumitomo Heavy Indus
`tries. Each of the immediately foregoing Japanese publica
`tions is incorporated herein by reference.
`0017 PCT Application Publication No. WO2004/004787,
`assigned to Universite Libre De Bruxelles—Hospital Erasme
`and incorporated herein by reference, discloses a method by
`which continuous measurement of radioactivity by dosimetry
`is eliminated. The disclosed method requires an initial cali
`bration step but thereafter, radiation dose is calculated based
`on the predictable decay of radioactivity as a function of time.
`Japanese Publication No. JP2004-290455, assigned to
`Nemoto Kyorindo KK, discloses a radiation-shielded injector
`system which withdraws FDG from prefilled syringes and
`allows other fluids such as saline to be administered. Euro
`pean Application Publication No. EP 1616587, assigned to
`University of Zurich and incorporated herein by reference,
`discloses a radioactive fluid dispensing device that pushes
`FDG into tubing within a radiation dose calibrator prior to a
`saline injection that administers the FDG to the patient.
`United States Patent Application Publication Nos. 2005/
`0203329 and 2005/0203330 to Mute et al. disclose a robotic,
`automated system for extracting radioactive fluids from a vial
`or bulk container into a nu