Patent Description:
The present disclosure generally relates to nuclear medicine, and specifically concerns mobile <NUM>Sr/<NUM>Rb elution system.

The subject matter disclosed herein relates to radiopharmaceutical substances with a short half-life like Rubidium (<NUM>Rb). Rubidium (<NUM>Rb) is used as a positron emission tomography (PET) tracer for non-invasive determination of myocardial perfusion (blood flow).

<NUM>Sr/<NUM>Rb elution systems typically comprise a reservoir of sterile saline solution (e.g. <NUM>% Sodium Chloride Injection), a pump system to push the sterile saline solution from a reservoir, a source for generating radioactive isotopes in solution, a radioactivity detector to measure activity of different isotopes, a dose calibrator, a waste container, a set of infusion tubing assembly, one or more sensors, a computer, and shielded enclosures on a platform for transporting the elution system. During operation, the pump moves saline solution from the reservoir and through the generator in order to elute the <NUM>Rb in the form of <NUM>RbCl, and also to regulate the flow of sterile saline solution to a bypass line. The radioactive solution which comes out from the generator is then infused to a patient to be diagnosed via a patient outlet. As known in the art, <NUM>Rb is generated by radioactive decay of <NUM>Sr, and thus the rate of production of <NUM>Rb at any given time is a function of the activity of <NUM>Sr remaining in the generator. The rate of <NUM>Rb production exponentially decreases through the useful life of the generator, in direct correlation with the half-life of <NUM>Sr.

The various shielded and non-shielded components in the elution system play a pivotal role in providing a desired dose and ensuring that no radioisotope breakthrough occurs during the elution process. Cardiogen-<NUM>® and RUBY-FILL® are known <NUM>Sr/<NUM>Rb generator systems and represent system where the dose calibrator is either not included or included within the cabinet structure. There is a need for providing the dose calibrator outside the main cabinet structure and to ensure that such configurations are safe for the user and for the patient. Outside dose calibrator may advantageously remain out high dose radioactivity fields and at a stable location so as to maintain precision of its radioactivity detection.

<CIT> describes an infusion system which may include a strontium-rubidium radioisotope generator that generates a radioactive eluate via elution, a beta detector, a gamma detector, and a controller. The beta detector and the gamma detector may be positioned to measure beta emissions and gamma emissions, respectively, emitted from the radioactive eluate. In some examples, the controller is configured to determine an activity of rubidium in the radioactive eluate based on the beta emissions measured by the beta detector and determine an activity of strontium in the radioactive eluate based on the gamma emissions measured by the gamma detector.

<CIT> describes neurostimulation assemblies, systems, and methods which make possible the providing of short-term therapy or diagnostic testing by providing electrical connections between muscles and/or nerves inside the body and stimulus generators and/or recording instruments mounted on the surface of the skin or carried outside the body. The assembly affords maximum patient mobility and comfort through differentiated components having minimal profiles and connected by way of detachable and adjustable connections.

An object of the present disclosure is to provide new configurations of a <NUM>Sr/<NUM>Rb elution system wherein the dose calibrator is not within a main cabinet structure. Another object of the disclosure is to provide safety means that are adapted to these new configurations of a <NUM>Sr/<NUM>Rb elution system.

Other obj ects, advantages and features of the present disclosure will become more apparent upon reading of the following non-restrictive description of specific embodiments thereof, given by way of examples only with reference to the accompanying drawings.

As used herein, the terms "elution system", "rubidium elution system" and "<NUM>Sr/<NUM>Rb elution system" can be used interchangeably and refer to a strontium-rubidium infusion system for use in generating a radioactive solution containing rubidium-<NUM>, measuring the radioactivity in the solution generated by the system, and infusing the radioactive solution to a patient in order to perform various studies on a patient's organ, such as heart or kidney.

As used herein, the terms "cart" or "system" or "trolley" are intended to encompass a platform. Said platform can be mobile or stationary.

As used herein, the terms "primary cart" or "primary mobile cart" refer to a first cart, which can include a first cabinet structure and/or a first platform.

As used herein, the terms "secondary cart" or "secondary mobile cart" refer to a second cart, which can include a second cabinet structure and/or a second platform.

The material used for "shielding" is made up of any radiation attenuating material, including, but not limited to, depleted uranium (U), lead (Pb), tin (Sn), antimony (Sb), tungsten (W), bismuth (Bi), any other material, or any combination thereof, as long as it provides a barrier to the radioactivity of rubidium or strontium.

As used herein, the term "shielded component" refers to components of the system that are surrounded by a shielding material, and may refer to the generator, the dose calibrator, the activity detector, the waste container, and/or the tubing line or a part of the tubing line.

As used herein, the term "non-shielded components" refers to components of the system that are not shielded, such as the pump, the valves, the saline reservoir, the computer, the controller of the system, the interface of the dose calibrator, and/or the tubing line or a part of the tubing line.

As used herein, the term "cabinet structure" refers to an outer structure of the system that extend upward from a platform and houses an assembly. The cabinet structure may be formed of any radiation resistant material, including, but not limited to, stainless steel, injectionmolded polyurethane, or any other suitable materials or combination thereof.

As used herein, the expression "locking means for preventing access to the interface by a user of the system" refers to any mechanism, system, or technology to provide security against access by a user to the interface, such as a locked compartment enclosing the interface of the dose calibrator, the requirement for input of a security code or security data (RFID, biometric, numeric, audible, or the like) for modifying the parameters of the interface, integrating the interface into the dose calibrator in such a way that the interface is rendered not accessible, or the like. In an embodiment, only the manufacturer have access to the interface of the dose calibrator. In another embodiment, no one has access to the interface. Being placed outside the primary assembly, the dose calibrator is therefore accessible and it is advantageous to prevent a user from modifying the interface parameters in order to ensure that the dose calibrator remains set properly for the rubidium elution system of the present disclosure.

As used herein, the term "electronic communication" refers to any electronic transmission or exchange of information, such as a user's commands, configuration of parameters and measurements. The electronic communication between the interface of the dose calibrator and the computer, ensures that measurements taken by the dose calibrator are transferred to the computer, and that said measurements are coordinated with the elution of the sample to be tested by the dose calibrator.

As used herein, the term "supporting accessories" refers to items such as wheels, lever, paddle, additional saline reservoir, drawer system for housing vials, and a handle for facilitating movement of the system.

The generator column may be prepared in accordance with <CIT>.

The generator system should be able to perform all the desired functions without unwanted and hazardous effects. <NUM>Rb has a half-life of <NUM> seconds, and its potential impurities, <NUM>Sr and <NUM>Sr, have a half-life of <NUM> days and <NUM> days, respectively. It is essential that patients are not exposed to these undesired isotopes, of which both are characterized by a long half-life. Accordingly, in order to ensure adequate safety, quality control testing of the generator is performed on daily basis prior to use. The daily quality control process for the generator includes collecting an eluted sample in a shielded vial for evaluation, and measuring the activity of the sample in a dose calibrator. Further, the sample is retained to permit decay of all active rubidium, after which a second stage of breakthrough testing is performed. The measured initial activity and the final activity are used to calculate the breakthrough information. The United States Pharmacopeia (USP) provides relevant regulatory limits for breakthrough of strontium of <NUM>µCi of <NUM>Sr/ mCi of <NUM>Rb activity and <NUM>µCi of <NUM>Sr/ mCi of <NUM>Rb activity. Further, to ensure a higher degree of safety, a system may impose a more stringent limit of <NUM>% of the USP limits.

A constant activity-rate refers to an activity-rate delivered with respect to time wherein the activity-rate is constant with respect to a predetermined constant activity concentration. A method to deliver a constant activity-rate dose is described in <CIT> ,.

Different elution strategies that can be used for patient infusions include:.

In an embodiment of the present disclosure, the rubidium elution system includes a controller configured to control the pump and the at least one valve so as to deliver a solution of rubidium at a constant activity rate to a patient. Said controller is preferably included in the primary assembly and carried on a first platform.

<FIG> shows a front view of a rubidium elution system according to the present disclosure. The elution system <NUM> comprises of two mobile platforms <NUM> and <NUM>, either or both platforms <NUM> and <NUM> can be manually or motor driven. In this embodiment, each of platforms <NUM> and <NUM> has two pairs of wheels <NUM> mounted on a bottom side of the platforms <NUM> and <NUM>, in order to allow the mobility of the system. The first cabinet structure <NUM> includes a front door <NUM> (shown in <FIG>) that can be opened in order to access the generator <NUM>, tubing circuit and other components. The tubing circuit includes an eluant line <NUM> that provides an eluant (preferably a saline solution contained in a saline reservoir <NUM>) to the generator <NUM> by means of a pump <NUM>. The tubing circuit also includes a bypass line <NUM> connected to the eluant line <NUM> that carries the eluant to the tubing circuit downstream the generator <NUM> such that the eluant bypasses the generator <NUM>. The tubing circuit further includes a waste line <NUM> that directs into a waste container <NUM> a mixture composed of the eluant fed by the bypass line <NUM> and the radioactive eluate that has exited the generator <NUM>. The tubing circuit also further includes a patient line <NUM> that directs the same mixture to either i) a patient for infusing said patient with a rubidium solution, or ii) a vial located in the dose calibrator <NUM> for system's calibration and strontium breakthrough test. The activity detector <NUM> can be a beta detector, a positron detector, or a beta and positron detector.

In certain embodiments, the pump system comprises a pump <NUM> that can be embodied by a syringe pump, a peristaltic pump, another type of pump, or a combination thereof.

In the embodiment, the top surface of a compartment housing the waste container <NUM> is lower than the top surface of the compartment housing the generator <NUM>, as illustrated in <FIG>. In another embodiment, the waste container can be at the same elevation than the generator <NUM>. In a further embodiment, the top surface of a compartment housing the waste container <NUM> is higher than the top surface of the compartment housing the generator <NUM>, as illustrated in <FIG>.

<FIG> provides a front view of a rubidium elution system, wherein the rubidium elution system <NUM> comprises a first and a second assemblies, and each assembly is housed within a first cabinet structure <NUM> and a second cabinet structure <NUM>, respectively. In this system, both cabinet structures <NUM> and <NUM> are positioned on a single platform <NUM>, which is advantageously mobile. Said platform <NUM> can be manually or motor driven. The platform <NUM> has preferably two pair of wheels <NUM> mounted on a bottom side of the platform <NUM>, in order to allow mobility of the system. The second cabinet structure <NUM> is an optional element of this system. More particularly, a variant of this system is envisioned where the dose calibrator stands beside the first cabinet structure on the single platform. A handle <NUM> is advantageously provided for manual displacement of the system. The handle <NUM> can be located on the first cabinet structure <NUM> (not illustrated), on the second cabinet structure <NUM> as shown in <FIG>, or on the platform (not illustrated).

<FIG> provides a front view of a further embodiment of the rubidium elution <NUM> system of the present disclosure, where the single platform <NUM> has three pairs of wheels <NUM> that are preferably mounted on a bottom side of the platform <NUM>.

<FIG> illustrates of another embodiment of the rubidium elution system <NUM> of the present invention, which includes a mobile first platform <NUM> and a mobile second platform <NUM>. In this embodiment, the waste container <NUM> is at an elevation higher than the elevation of the generator <NUM>. The rubidium elution system <NUM> of the present disclosure preferably includes and an activity detector <NUM> that is represented with a box for sake of simplicity in <FIG>. The activity detector <NUM> allows the detection and measurement of the radioactivity in the tubing circuit. Preferably, the activity detector <NUM> is positioned downstream the generator <NUM> and the bypass line <NUM> in order to measure the radioactivity of the mixture of the radioactive eluate exiting the generator <NUM> with the bypassed eluant. The circulation of the fluid (eluant and eluate) in the tubing circuit is obviously ensured via the use of valves <NUM>. Preferably, said at least one valve <NUM> comprises a valve upstream the generator <NUM> and a valve downstream the generator <NUM>.

<FIG> provides a view of an alternative rubidium elution system <NUM>, where the dose calibrator <NUM> is positioned on a stationary second platform <NUM>. In <FIG>, the stationary second platform <NUM> is embodied by a stool for sake of the illustration. However, the stationary second platform <NUM> can be a benchtop, a desk, a table, a kiosk, a countertop, or any other fixed location. The dose calibrator <NUM> and its shielded compartment are relatively heavy and there is an advantage for the user to move the rubidium elution system <NUM> without the dose calibrator <NUM>. Since the dose calibrator <NUM> is a sensitive apparatus, positioning the dose calibrator at a fixed location represents an additional benefit. The dose calibrator <NUM> is enclosed in a shielded compartment composed of multiple rings of lead positioned on top of each other in order to form a tubular compartment upwardly opened. The illustrations of <FIG> show the pile of lead rings and it should be understood that the dose calibrator <NUM> is located inside these rings of lead. The lead rings provide a strong barrier to radioactivity emission from inside (the sample) and from outside (the surrounding elements containing rubidium and/or strontium). Therefore, the dose calibrator compartment composed of lead rings prevents any interference coming from the surrounding elements with the radioactivity of a sample located inside the lead rings for calibration test and/or breakthrough test.

For the purpose of the breakthrough tests and calibration tests, the primary assembly is preferably placed close to or adjacent to the dose calibrator <NUM>. The computer of the system can communicate with the dose calibrator <NUM> via a network (that may optionally include Wi-Fi), via a wireless connection (e.g. Bluetooth) or via a direct electronic connection (e.g. Ethernet, USB or serial cable). For the quality control and calibration tests, a sample of rubidium solution is collected in a vial that is located in the dose calibrator by means of the patient line. In a preferred embodiment, when the dose calibrator <NUM> is connected to the computer by an electronic cable, said cable is equipped with a breakaway connector. In a preferred embodiment, the breakaway connector is a magnetic connector. An example of a magnetic connector is the Male and Female Magnetic Connector manufactured by Rosenberger Group, Germany, which is illustrated in <FIG> and <FIG>. More particularly, <FIG> shows one section <NUM> of the cable having the male portion <NUM> of the magnetic connector and a connector <NUM> for connecting the interface. <FIG> shows the other section <NUM>'of the cable having the female portion <NUM> of the magnetic connector and a connector <NUM> for connecting the computer. It should be understood that the present disclosure encompasses other types of breakaway connector that have the ability to detach when the primary assembly is moved away from the dose calibrator. When the cable <NUM> is connected to the dose calibrator <NUM> through an interface, said interface is preferably solidly attached to the dose calibrator so that pulling on the cable section <NUM>' results in disconnecting both portions <NUM> and <NUM> of the breakaway connector.

According to the embodiments, the first and second platforms <NUM> and <NUM> are mobile and are removably attached to each other. The attachment <NUM> can be achieved through the attachment <NUM> of the cabinet structures <NUM> and <NUM> (indirect attachment as represented in <FIG> and <FIG>) or the attachment can be achieved by the attachment of the platforms <NUM> and <NUM> together (direct attachment - not shown). The removable attachment <NUM> is schematically represented by two solid lines in <FIG> and <FIG>. For the purpose of this embodiment, any removable attaching means known by a skilled technician can be used. In an embodiment, the dose calibrator is housed in a second cabinet structure <NUM>. In another embodiment, the dose calibrator is partially housed in a second cabinet structure. In further embodiment, there is no second cabinet structure housing the dose calibrator. In an embodiment, the first and second cabinet structures <NUM> and <NUM> are removably attached together so as to move the first and second platforms together. In alternate embodiment, the first and second cabinet structures <NUM> and <NUM> can be moved independently from each other. In this embodiment, the attachments <NUM> preferably provide sufficient flexibility to move the cabinet structures <NUM> and <NUM> independently from each other.

In some embodiments, the <NUM>Sr/<NUM>Rb generator, the dose calibrator, the waste container, and the activity detector are each enclosed within respective shielded compartments. Preferably, each of the <NUM>Sr/<NUM>Rb generator, the dose calibrator, the waste container, and the activity detector is enclosed within respective shielded compartments. The door <NUM> of the waste compartment <NUM> is preferably shielded. The opening of the generator is also preferably shielded.

In another aspect, the second platform <NUM> include an optional storage compartment, such as a space, tray, drawer, or bin for carrying one or more additional components. Such additional components may include supplies that can include, but are not limited to, tubing for the dose calibrator, vials for the dose calibrator, and other related medical supplies.

In another aspect, the waste container <NUM> is housed within an enclosure (shown in <FIG>) that may be removed from its shielded compartment <NUM>. In embodiments, the waste container compartment <NUM> can be accessed by opening a side door <NUM> of the first cabinet structure <NUM> in the configurations of <FIG>, or by opening a top panel <NUM> of the first cabinet structure <NUM> as shown in <FIG>. In a certain embodiment, the waste container <NUM> can be accessed from the waste container compartment <NUM> horizontally by mounting a waste platform on rails. In this embodiment, the waste platform is slid out horizontally prior to pulling out the waste container <NUM> from its compartment. In another compartment, the waste container <NUM> is removed by a lifting mechanism that can be automated.

In certain embodiments, at least one of the first and second platforms <NUM> and <NUM> includes wheels for allowing the mobility thereof, and a mechanism for braking and locking the wheels, such as a lever.

In other aspects, the computer of the rubidium elution system is configured to proceed with a quality control test (breakthrough tests) at pre-determined time, upon user's request and at least once a day. The computer is configured to prevent a patient infusion when the quality control test result determines that the strontium concentration is equal to or above <NUM>µCi of <NUM>Sr/ mCi of <NUM>Rb activity or equal to or above <NUM>µCi of <NUM>Sr/ mCi of <NUM>Rb activity.

In accordance with the presently disclosed subject matter, the dose calibrator <NUM> is outside the primary assembly. The present disclosure includes embodiments where the dose calibrator is accompanied with its own interface that configures the dose calibrator for detection of rubidium, and with embodiments where the calibrator has no interface and is controlled by the computer. When the dose calibrator is accompanied with its own interface, said interface may be accessible to a user and therefore, there is a need for preventing a user from reconfiguring the interface of the dose calibrator <NUM>. As such, in certain preferred embodiments, the system further includes a locking means for preventing a user from reconfiguring the dose calibrator in such a way that the dose calibrator remains configured as initially configured by the manufacturer. In a preferred embodiment, the dose calibrator is configured to detect rubidium and/or strontium. In a further preferred embodiment, the dose calibrator is configured to detect rubidium. Since strontium and rubidium are in an instant equilibrium, one can use the measured quantity of rubidium to calculate the quantity of strontium that is present in a solution after the initial content in rubidium has decayed. On way to prevent a user from reconfiguring the dose calibrator is to prevent access to the interface of the dose calibrator. In an embodiment, the locking means comprises an identification system for allowing access to the interface and reconfiguring the dose calibrator by the manufacturer of the system and not the user of the system. In another embodiment, the locking means comprises a locked compartment <NUM> as shown in <FIG> and <FIG>, which encloses the interface of the dose calibrator <NUM> and prevents access to by the user of the system. Preferably, the manufacturer of the system remains able to unlock the compartment of the interface and able to configure or reconfigure the dose calibrator as needed. In a variant of this embodiment, the locked compartment enclosing the interface of the dose calibrator <NUM> is provided by a second cabinet structure <NUM> that also encloses or partly encloses the dose calibrator <NUM>. The compartment enclosing the interface can be i) included in the primary assembly, ii) integrated in the dose calibrator, iii) contained a secondary assembly that includes the dose calibrator, or iv) separated from the primary assembly and the dose calibrator. In a further embodiment, there is no interface, and the computer does not allow the user to modify the configurations of the dose calibrator.

In another aspect of the present disclosure, the rubidium elution system <NUM> comprises a computer screen <NUM> (shown in <FIG>) includes a speaker for providing an audible or visible alert for one or more different operations of system.

In another aspect of the present disclosure, the rubidium elution system <NUM> comprises a computer that comprises a processor, and a memory communicatively connected to the processor when the system is functioning, as well as processor-executable instructions, that, when executed on the processor, cause the system to perform representative functions of the system. Additionally, certain embodiments may be implemented as computer-executable instructions stored on computer-readable storage media. Computer readable storage media may be distinguished from computer-readable communications media that include transitory signals.

Claim 1:
A rubidium elution system (<NUM>) comprising:
a. a primary assembly including a <NUM>Sr/<NUM>Rb generator (<NUM>), an activity detector (<NUM>), a waste container (<NUM>), a pump system, a sensor, a tubing circuit, at least one valve (<NUM>), and a computer; wherein the primary assembly is housed in a first cabinet structure (<NUM>); and
b. a dose calibrator (<NUM>) that is located outside the first cabinet structure, wherein the dose calibrator and the computer are in electronic communication;
characterised in that the primary assembly is positioned on a first platform (<NUM>), and the dose calibrator is positioned on a second platform (<NUM>); and wherein the first platform and the second platform are mobile; and wherein:
(i) the first and second platforms are removably attached together in order to permit movement of the first platform together with the second platform; or
(ii) the dose calibrator is housed or partly housed in a second cabinet structure (<NUM>), and the first and second cabinet structures are removably attached together so as to permit movement of the first platform together with the second platform.