Abstract:
A method of delivering a radioactive liquid includes, performing an initialization, including; extracting at least a first amount of a radioactive liquid from a source of radioactive liquid, measuring a radioactivity level for the first amount of radioactive liquid, and performing a calibration phase. The calibration phase includes, extracting a second amount of radioactive liquid from the source of radioactive liquid wherein the second amount is calculated based on the radioactivity level of the first amount to provide a total dose of radioactive liquid having a predetermined radioactivity level, and delivering the total dose and performing at least one more calibration and delivery phases.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation application of U.S. patent application Ser. No. 14/505,861, filed Oct. 3, 2014, now granted U.S. Pat. No. 9,295,857, which is a continuation of U.S. patent application Ser. No. 13/965,670, filed Aug. 13, 2013, now granted U.S. Pat. No. 8,852,071, which is a divisional application of U.S. patent application Ser. No. 11/572,123, filed Oct. 15, 2008, now granted U.S. Pat. No. 8,517,905, which claims priority to PCT Application No. PCT/CH2005/000403 filed Jul. 14, 2005, expired, which claims priority to EP application No. 04405459, filed Jul. 16, 2004. 
    
    
     BACKGROUND OF THE INVENTION 
     The present invention relates to a device and a method for dispensing, a radioactive liquid to a destination. In particular, the invention relates to the problem of accurately dispensing a well-determined dose of radioactivity, e.g., for injection to a living body. 
     In a number of medical applications, it is necessary to, deliver a radiopharmaceutical containing a radionuclide to a patient. Due to the ionizing radiation emitted by the radionuclide, such pharmaceuticals pose a danger to both the patient and the personnel administering the radiopharmaceutical if not handled properly. 
     Examples for diagnostic uses of radiopharmaceuticals include positron emission tomography (PET) and single-photon emission computerized tomography (SPECT). In these methods, a patient is injected a dose of a radiopharmaceutical which can be absorbed by certain cells in the brain or in other organs. The concentration of the accumulated radiopharmaceutical in a specific body part will often depend on factors of diagnostic interest, such as cell metabolism or other physiological or biochemical processes. Thus, such processes can be imaged in a non-invasive fashion by determining the spatio-temporal distribution of radioactivity within the body part of interest. In PET, this is achieved by monitoring pairs of temporally coincident gamma rays emitted in opposite directions resulting from the annihilation of positrons, which are emitted through beta-plus decays of the (proton-rich) radionuclide. The most common radionuclides radioisotopes) for use with PET are  15 O,  18 F,  11 C,  13 N and  82 Rb. Radiopharmaceuticals of interest for PET include, but are not limited to, substances like [ 15 O]—H 2 O, [ 18 F]-fluorodeoxyglucose ([ 18 F]-FDG), [ 18 F]-fluoromisonidazole ([ 18 F]-FMISO), [ 11 C]-labeled amino acids, [ 13 N]-ammonia etc. 
     The most common therapeutic uses of radiopharmaceuticals are the  131 I therapies in thyroid diseases. 
     In these applications, it is desirable to administer an exactly determined dose of radiopharmaceutical to the body. Often the radiopharmaceutical is delivered in a vial from which it has to be dispensed into individual patient doses. In many centers this is a manual process done by the technical personnel. Since the concentration of the radiopharmaceutical in the vial can be very high, the manual dispensing is associated with considerable radiation burden to the hands. Furthermore the accuracy of the manual dispensing is limited and dependent on the experience of the person in charge. 
     As an example, U.S. Pat. No. 4,410,108 discloses a syringe shield equipped with a radiation detector. A liquid radiopharmaceutical is drawn from a vial into the barrel of a syringe placed within the syringe shield, while the level of radioactivity within the barrel is monitored by the radiation detector. In this way, an aliquot of the radiopharmaceutical having exactly the required dose of radioactivity can be drawn into the syringe. Subsequently, the syringe with its shield is manually removed from the vial, and the radiopharmaceutical is injected to the patient. This device is unsatisfactory in requiring manual transfer of the syringe after it has been filled with the radiopharmaceutical, as this may expose the personnel handling the syringe to ionizing radiation. Although the half-life of the radiopharmaceutical is usually rather short and the applied dosages are themselves not harmful, constant and repeated exposure over an extended period of time can be harmful. 
     A number of techniques have been proposed to reduce exposure by minimizing the time of exposure of personnel, by maintaining distance between personnel and the source of radiation, and by shielding personnel from the source of radiation. As an example, European patent application EP 0 486 283 discloses a system for delivering H 2   15 O. A collection bottle is filled with saline, then a fluid stream comprising H 2   15 O is passed through the collection bottle while the activity in this bottle is monitored by a radiation detector. When a desired level of radiation is reached, the liquid in the bottle is transferred to a motor-driven syringe and then injected to the patient body. U.S. patent application publication No. 2003/0004463 also discloses a system for dispensing a radiopharmaceutical in a remote fashion, without the need of manual intervention. The radiopharmaceutical is drawn from a vial into a syringe surrounded by a radiation detector, and the level of radioactivity in the syringe is determined. Through specially adapted tubing and valves, the radiopharmaceutical is subsequently delivered to a patient without the need of moving the syringe to another location. 
     While these systems obviate the need of manual handling of a syringe, they tend to be imprecise in situations where small amounts of radioactive liquid, possibly with a very high concentration of activity, need to be handled, due to the presence of dead volumes. By the way of example, the radiopharmaceutical may come in a vial at an activity concentration of 2 GBq/ml (one billion Becquerels per milliliter). If the required activity for injection to the patient is, say, 100 MBq, a volume of just 50 microliters needs to be transferred from the vial to the patient. Such small amounts of liquid are difficult to handle with the systems of the prior art. 
     U.S. Pat. Nos. 4,562,829 and 4,585,009 disclose strontium-rubidium infusion systems equipped with an in-line radiation detector. A radiopharmaceutical exiting a strontium-rubidium generator flows past the radiation detector, which monitors the activity of the radiopharmaceutical in passing. From there, the radiopharmaceutical is either administered to a patient or is sent to waste. In U.S. Pat. No. 4,409,966, a flow of patient blood is shunted through a radiation detector during injection of the radiopharmaceutical, and the level of radioactivity in the blood is monitored. Also with such systems, it is difficult to administer an exactly determined dose, especially for concentrated radiopharmaceuticals with high specific activities, as the volume of the tubing already may exceed the desired volume to be injected. 
     SUMMARY OF THE INVENTION 
     It is therefore an object of the invention to provide a device which is capable of accurately dispensing a desired level of radioactivity in a liquid, and which may be operated remotely. 
     Thus, according to the invention, a source of a radioactive liquid and a source of a flushing liquid can be selectively connected to a fluid delivery path by way of valve means. An activity metering unit is operable to determine a level of radioactivity in a metering section of the fluid delivery path downstream from the valve means. In this way, it is possible to provide some amount, even a very small amount, of the radioactive liquid to a section of the fluid delivery path adjacent to the valve means. The flushing liquid can then be used to flush this amount of radioactive liquid to the metering section, where its activity can be determined and further steps to be taken can be decided based on this determination of activity. By use of valve means adapted for remote control (e.g. an electromagnetically or pneumatically operated valve), operation of the inventive device can be performed remotely. 
     It is a further object of the present invention to provide a method of operation of such a device. 
     Thus, according to the invention, the device is operated by transporting a first amount of radioactive liquid to the metering section, using the activity metering unit to measure a reference level of radioactivity, calculating a second amount of the radioactive liquid still to be delivered such that the first and second amounts of radioactive liquid together have some predetermined level of radioactivity, and delivering the first and second amounts of radioactive liquid to the destination. In this way, it is possible to deliver an exactly known level of radioactivity to the destination, independent of the activity concentration of the radioactive liquid. Preferably, the first amount of radioactive liquid is between 20% and 80% of the sum of the first and second amounts of radioactive liquid, more preferably between 30% and 70%, most preferably between 40% and 60%. In this way, high precision can be achieved. 
     In an advantageous embodiment of the inventive device, the device additionally comprises a control unit. The unit receives signals from the activity metering unit and controls operation of the valve means between at least two states. In the first state, the source of radioactive liquid is connected to the fluid delivery path for flow of the radioactive liquid into the fluid delivery path. In the second state, the source of flushing liquid is connected to the fluid delivery path for flow of flushing liquid into the fluid delivery path. If any other actively driven components are present in the device, such as additional valves or pumps, they may also be controlled by the control unit. 
     Advantageously, second valve means are provided downstream from the metering section for directing flow in the fluid delivery path either to the destination or to a waste reservoir. In this way it is avoided that the destination receives excessive amounts of flushing liquid during operation of the device, and in case of malfunctioning of components of the device, the radioactive liquid can be dumped to the waste reservoir. 
     Advantageously, a first and/or a second pump are provided for pumping the radioactive liquid or the flushing liquid, respectively, through the first valve means and into the fluid delivery path. Preferably, the first pump and/or the second pump is operable to receive a control signal and to deliver a predetermined volume of liquid based on the control signal. In this way, exactly known amounts (volumes) of the radioactive liquid and/or of the flushing liquid can be dispensed to the fluid delivery path. 
     The fluid delivery path may comprise a fill-in section extending from the first valve means to the metering section. Advantageously, the metering section is capable of holding a fluid volume which is at least three times, more preferably at least five times the volume of the fill-in section. This enables the metering section to hold at least two, preferably three, fractions of radioactive liquid, each with a volume up to the volume of the fill-in section, plus the flushing liquid required to flush these fractions into the metering section. Thereby, the total activity of two, preferably three, fractions of radioactive liquid may be determined in a single measurement by the activity metering unit. 
     Advantageously, the device is adapted for delivering a radiopharmaceutical for injection to a living body for delivering the radiopharmaceutical to an injection needle). This encompasses, among other things, the use of compatible materials, which most be resistant to the radiopharmaceutical and the flushing liquid (usually saline solution in this case), and which must be able to withstand sterilization procedures. Such materials are well known. 
     As used herein, the term “pharmaceutical” refers to any substance to be injected or otherwise delivered into the body (either human or animal) in a medical procedure and includes, but is not limited to, substances used in imaging procedures and therapeutic substances. The term “radiopharmaceutical” refers to any pharmaceutical emitting ionising radiation by radioactive decay. 
     Further advantageous embodiments of the invention are laid down in the dependent claims. In particular, the inventive method may comprise an additional initialization procedure, in which an offset amount of radioactive liquid is transported to the metering section, an offset level of radioactivity is determined, and the predetermined level of radioactivity for the main procedure is determined from this offset level and a desired level of radioactivity to be dispensed. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The invention will be described in more detail in connection with an exemplary embodiment illustrated in the drawings, in which 
         FIG. 1  shows a schematic and simplified illustration of a device according to the present invention; 
         FIG. 2  shows a schematic and simplified illustration of a dose calibrator; 
         FIGS. 3A and 3B  show simplified illustrations of a pinch valve; 
         FIG. 4  illustrates a first state of operation of the device of  FIG. 1 ; 
         FIG. 5  illustrates a second state of operation of the device of  FIG. 1 ; 
         FIG. 6  illustrates a third state of operation of the device of  FIG. 1 ; 
         FIG. 7  illustrates a fourth state of operation of the device of  FIG. 1 ; 
         FIG. 8  illustrates a fifth state of operation of the device of  FIG. 1 ; 
         FIG. 9  shows a flow diagram of a process according to the present invention; and 
         FIG. 10  illustrates the levels of activities measured in various stages of the process of  FIG. 9 . 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       FIG. 1  shows, in a highly schematic manner, a device for dispensing a radioactive liquid according to a preferred embodiment of the present invention. The device is designed for dispensing a radiopharmaceutical for injection to a patient. 
     The radiopharmaceutical  1  is provided in a vial  2 . In order to protect the surroundings from radioactivity originating from the vial  2 , the vial  2  is placed inside a shield  3 . Suitable vials and shields for various kinds of radiopharmaceuticals are well known in the art and are available commercially. 
     A section  4  of tubing, comprising a needle at its end for puncturing a septum closing off vial  2 , extends from the inside of vial  2  through a first peristaltic precision pump P 1  and to a first three-way pinch valve V 1 . At its first port “a”, the valve V 1  is connected to the section  4  of tubing from the vial  2 ; at its second port “b”, it is connected to a section of tubing  7  extending from the valve V 1  to an activity metering unit  9  (in the following shortly called a “dose calibrator”). The third port “c” is connected to a section  6  of tubing leading from a saline reservoir  5  through a second peristaltic precision pump P 2  to the valve V 1 . The valve V 1  is operable to connect port “a” with port “b” or to connect port “c” with port “b”. 
       FIGS. 3A and 3B  illustrate, in a highly schematic manner, the mode of operation of the pinch valve V 1  as advantageously used in the present embodiment. A sliding element  31  can be moved up or down, pressing either on an upper or on a lower section of flexible tubing which is passed through the pinch valve. Thereby, either port “c” or port “a” is closed off from port “b”, and the other port is connected to port “b”. The sliding element  31  may, e.g., be operated electromechanically or pneumatically. A similar pinch valve is used as valve V 2 . Such pinch valves are advantageous because no moving parts get into contact with the liquid within the tubing. Thus the valve cannot get contaminated by radioactive liquid possibly present in the tubing. 
     The pumps P 1  and P 2  are preferably peristaltic precision pumps. In a peristaltic pump, a section of flexible tubing is passed through the pump unit. Fluid is forced along the tubing by waves of contraction produced mechanically on the flexible tubing. Peristaltic pumps offer the advantage that the liquid is always contained in the tubing, and no moving parts get into contact with the liquid to be delivered. Thus the pump itself cannot be contaminated by radioactive liquid present in the tubing. By the use of peristaltic pumps and pinch valves, the connections from the saline reservoir  5  to the metering section  7  and from the vial  2  to the metering section  7  may consist of a single piece of flexible tubing each, which can be easily replaced in regular intervals to avoid cross-contamination, without the need to replace the much more expensive pump and valve assemblies themselves. 
     The section  7  of tubing may be called a “fill-in section”. This fill-in section  7  is connected to a section  8  of tubing placed inside the dose calibrator  9 , section  8  being called a “metering section”. The metering section  8  is relatively long, providing a volume of at least five times the volume of the fill-in section, by having a meander-like shape or preferably, a coil shape as illustrated for a metering section  8 ′ in  FIG. 2 . A coil shape is preferred in practice because it minimizes pressure losses during fluid flow. The meander-like shape has been chosen in  FIGS. 1 and 3-7  for illustrative purposes. 
     The tubing exits the dose calibrator  9  and connects to the first port “d” of a second three-way valve V 2 . The second port “e” of this valve is connected to a section  10  of tubing leading to an injection needle  11 , only crudely symbolized by a triangle in  FIG. 1 . The third port “f” of valve V 2  leads to a waste reservoir  12 . The waste reservoir  12  is preferably shielded, as radioactivity may enter in operation. 
     The dose calibrator  9  is connected to a controller  13  and provides signals to the controller  13  which are indicative of the level of activity within the dose calibrator  9 . The outputs of the controller  13  are connected to the pumps P 1  and P 2  as well as to the valves V 1  and V 2  for control of these. 
     A method of operation of the device is illustrated in  FIGS. 4 to 8  and symbolized in a flow diagram in  FIG. 9 . Operation can generally be divided into five phases: in an initialisation phase  910 , the device is brought into a well-defined initial state. In a calibration phase  920 , steps are performed for calibrating the radioactivity in vial  2 . In a delivery phase  930 , the radiopharmaceutical is delivered to the destination. In a step  940 , it is decided whether another injection shall be performed. If yes, operation will continue again with the calibration phase  920 ; if not, a shutdown phase  950  will follow. 
     Before starting the operation, the operator will have to determine two quantities: the desired activity Ar to be injected to the patient, and the estimated concentration of activity in the vial (activity per unit of volume, expressed in MBq/ml), Cv. These data are provided to the controller  13 . Operation then starts with the initialisation period  910 . 
     The initialisation period  910  comprises the following steps: 
     Step  911  (Initial filling of radiopharmaceutical to point C): In a first step, the complete tubing is filled with saline, thereby excluding air from the tubing system. For this, valve V 1  is switched into a state connecting ports “c” and “b”, while valve V 2  connects “d” and “e”. Pump P 2  flushes saline up to point B (cf.  FIG. 4 ). Then the tubing section  4  is inserted into a vial containing saline Valve V 1  is brought into a state connecting ports “a” and “b”, while valve V 2  still connects “d” and “e”. Pump P 1  now flushes saline until the tubing is completely filled with saline from point A (cf.  FIG. 4 ) to the destination beyond valve V 2 , and air is thus completely purged from the system. The tubing section  4  is then inserted into the vial  2  containing the radiopharmaceutical. Valve V 1  is brought into a state connecting ports “a” and “b”, while valve V 2  connects ports “d” and “f”. Pump P 1  is operated to pump radiopharmaceutical  1  from inlet point A and past point B at valve V 1  to some point C in the fill-in section  7 . The volume of radiopharmaceutical between points B and C in the fill-in section  7  does not need to be known exactly; it suffices to ensure that the section of tubing from A to B is filled completely with radiopharmaceutical, and that the activity in the volume between B and C is not larger than the desired end activity Ar. The situation at the end of step  911  is illustrated in  FIG. 4 , where the volume of radiopharmaceutical between points B and C is designated by reference number  21 . 
     Step  912  (Flushing of offset volume to dose calibrator): Valve V 1  is now switched to a state in which it connects ports “c” and “b”. Pump P 2  is operated to pump saline from the saline reservoir  5  towards valve V 1 . The volume to be pumped is slightly larger than the volume in the fill-in section  7  of the tubing, i.e. slightly larger than the volume between points B and D. This volume need not be known exactly. Thereby, the “offset volume”  21  is moved into the metering section  8 . The situation at the end of this step is illustrated in  FIG. 5 . 
     Step  913  (Initial determination of activity): The activity of volume  21  in the metering section  8  is measured by the dose calibrator  9  (measurement M 1 ). This activity will be called the “offset activity” A 1 . The controller  13  now calculates the missing activity Am required to reach a total activity of Ar: Am=Ar−A 1 . This is illustrated in  FIG. 10  in the leftmost column. From this and the estimated concentration of activity in the vial, Cv, the estimated missing volume Va 1  still to be delivered is calculated: Va 1 =Am/Cv. It is important to note that this calculation is still based on the estimate of the concentration of activity in the vial, and the result cannot be expected to be highly accurate. It is further important to note that no knowledge about the offset volume  21  is required in this calculation. 
     This step concludes initialisation  910 . In the following calibration phase  920 , the following steps are performed: 
     Step  921  (Filling of radiopharmaceutical to point C′): Valve V 1  is switched to a state in which it connects ports “a” and “b”. Pump P 1  is operated to pump a volume Vc′ through valve V 1 , filling the fill-in section to point C′. This situation is illustrated in  FIG. 6 , where this volume is designated by reference number  22 . Volume Vc′ is chosen to be approximately half of the estimated missing volume Va 1 : Vc′=Va 1 / 2 . It is important to note that volume Vc′ is known exactly in system internal units. The exact nature of these units depends on the type of pump used, e.g., the units could be pump revolutions, pump cycles etc. If a volume flow meter is placed in-line with the pump, the units provided by the flow meter can be used as system internal units. Depending on the type of pump and the type of tubing, the resolution of volume in this step can be very small, and even small volumes can be delivered accurately. 
     Step  922  (Flushing of volume Vc′ to dose calibrator): Valve V 1  is switched to connect ports “c” and “b”. Pump P 2  is operated to pump slightly more than the volume between points B and D of saline through valve V 1 . Thereby, volume  22  (=Vc′) of radiopharmaceutical is moved into the metering section  8 . The situation at the end of this step is illustrated in  FIG. 7 . 
     Step  923  (Calibration of activity): The activity in the metering section  8  is measured by the dose calibrator  9  (measurement M 2 ). This activity level will be called A 2 . It corresponds to the sum of the offset activity A 1  and the activity of the volume Vc′, which will be called the “reference activity” Ac′. This is illustrated in the second column of  FIG. 10 . Now the activity concentration in the vial in system internal units, Cs, is calculated: Cs=Ac′/Vc′=(A 2 =A 1 )/Vc′. The system is now calibrated in system internal units. 
     Step  924  (Determination of volume Vc″): The activity Ac″ still required to reach a total activity of Ar is determined: Ac″Ar−A 2 . From this, the volume Vc″ still to be delivered is calculated in system internal units: Vc″=Ac″/Cs=(Ar−A 2 )/Cs=(Ar−A 2 )/(A 2 −A 1 )*Vc′. 
     This completes the calibration phase  920 . In the following delivery phase  930 , the following steps are performed: 
     Step  931  (Filling of radiopharmaceutical to point C″): Valve V 1  is switched to a state in which it connects ports “a” and “b”. Pump P 1  is operated to pump the volume Vc″ through valve V 1 , filling the fill-in section to point C″. This situation is illustrated in  FIG. 8 , where this volume is designated by reference number  23 . 
     Step  932  (Flushing of volume Vc″ to dose calibrator): Valve V 1  is switched to connect ports “c” and “b”. Pump P 2  is operated to pump slightly more than the volume between points B and D of saline through valve V 1 . Thereby, volume  23  (=Vc″) of radiopharmaceutical is moved into the metering section  8 . Optionally, the total activity in the metering section is now measured (optional measurement M 3 , see right column of  FIG. 10 ). It should correspond exactly to the total desired activity Ar, provided that the volume of the metering section is large enough to hold all three volumes  21 ,  22  and  23  within this section. The latter condition is can always be fulfilled if the volume of the metering section  8  is at least five times the volume of the fill-in section  7 . If a significant discrepancy is detected, the system is stopped. 
     Step  933  (Delivery to injection needle): Valve V 2  is switched to connect ports “d” and “e”. Pump P 2  is operated to pump at least the volume of the metering section  8 , plus the volume of the tubing from the metering section to the injection needle and of the injection needle itself, of saline through valve V 1 . Thereby, all liquid in the metering section  8  is flushed to the patient, and exactly the required dose of radioactivity is delivered to the patient. 
     This completes the delivery phase  930 . If another injection of the same radiopharmaceutical (to the same or a different patient) is required, operation continues by repeating the calibration and delivery phases  920  and  930 . Otherwise, operation stops by a suitable shutdown procedure, which may involve additional cycles of flushing with saline. 
     When repeating calibration phase  930 , no additional initialisation as in phase  910  is necessary, since the metering section  8  has been flushed with saline, and the radiopharmaceutical extends exactly to point B. No activity is present in the metering section  8 . Therefore, in the above calculations, A 1  can be set to zero in this case, and Am is set to Ar. No further changes are necessary. The three-phase procedure with phases  910 ,  920  and  930  now simplifies to a two-phase procedure with phases  920  and  930  only. 
     It will be appreciated that the device of the present invention and the associated method of operation provide a number of inherent safety features. Specifically, there is a high degree of redundancy in the operation of the device, such that even in case of failure of one component, such as a pump or a valve, it is impossible that more than the desired dose will be delivered to the patient. Specifically, by its design the system will only allow the dose present within the metering section  8  to be delivered to the patient. This is because during the actual delivery of the radiopharmaceutical there is no connection between the vial  2  and the fluid delivery line. The discrete nature of the sequential measurements of activity within the metering section  8  is another feature which increases safety: In step  932 , the activity in the metering section  8  is actually known beforehand, and measurement M 3  just serves to confirm that the right amount of activity is present in the metering section  8 . If significant discrepancies are detected between the expected result and the actual measurement, operation will be stopped immediately, and an alarm will be given. 
     It will also be appreciated that, in normal operation, no radiopharmaceutical will enter the waste reservoir  12 . Thus, generation of radioactive waste is minimized. 
     A device according to the present invention in the embodiment of  FIG. 1  has been set up and tested in practice. The device was assembled from standard components available commercially. For the tubing sections  4  and  6 , flexible tubing made from silicone with an inner diameter of 1.52 mm was used. The pumps P 1  and P 2  were peristaltic precision pumps (P 1 : Ismatec™ ISM 596B, P 2 : Arcomed™ Volumed™ mVp 5000). The valves V 1  and V 2  were electrically operated pinch valves available from Bio-Chem Valve Inc. The metering section  8 ′ of tubing had a coil shape with nine windings and a diameter of 3.5 cm, made from fluoro-ethylene-propylene. A Veenstra VDC  405  dose calibrator was used as activity metering unit/dose calibrator  9 . The complete assembly was shielded by a 5 cm lead shield. As a controller  13 , a standard personal computer (Compaq Armada E500) equipped with a standard interface card was used. The control algorithm was implemented in LabVIEW™, available from National Instruments™. 
     This embodiment is especially suitable for the use with radiopharmaceuticals typically used in PET and SPECT applications. The device has been used to deliver radiopharmaceuticals with activity concentrations as high as 1000 MBq/ml to patients, with an absolute precision of as good as 100 microliters and a relative precision of better than 2% of the total activity delivered to the patient. 
     From the above description, it is clear that numerous variations of the described device and method are possible, and the invention is in no way limited to the above examples. 
     While the method has been described in a way that the volume of the metering section  8  of tubing is large enough to hold at the same time all volumes of radiopharmaceutical to be injected together, the method can readily be adapted for use with a dose calibrator which measures only one of these volumes at a time. In this case, the activities A 1 , Ac′ and, optionally, Ac″ are measured directly and sequentially and need not be calculated. Both variants of the method have in common that the activity of a precisely known volume (in some arbitrary units) is measured, enabling determination of the activity concentration of the radiopharmaceutical. 
     The method can be extended to take into account the decrease of activity during the dispensing procedure, in a straightforward manner by calculating the decay during the (predetermined) time needed for the dispensing procedure. 
     The inventive device and method are not only useful for delivering a radiopharmaceutical to a human or animal body, but also in other applications, also of a non-medical nature, in which a precisely known amount of activity is to be delivered to some destination. Accordingly, many variations of the types of tubing, valves, pumps etc, are possible. Specifically, other pump types than peristaltic pumps may be used. In fact, while the use of pumps is preferred, pumps may be omitted if the vial  2 , the saline reservoir  5  or both are placed “top-down” in a position higher than valves V 1 , V 2  and the destination  16 . Fluid flow is then effected by gravity alone. Instead of pumps, flow meters should then be provided, yielding volume information to the controller  13 . 
     Different types of valves than the above-described two-way pinch valves may be used. Specifically, it may be advantageous to provide, as valve V 1 , a valve which can be switched to a third state such that liquid can flow between ports “a” and “c”. In this way, the sections of tubing between points A and B may be flushed with saline from reservoir  5 , without the need of inserting a vial with saline instead of the vial with the radiopharmaceutical during initialisation. 
     Any suitable activity detector may be used as a dose calibrator  9 . Such detectors include standard Geiger-Müller counters, scintillating counters etc., which should be calibrated to yield a sufficiently precise measure of the actual activity in the metering section  8 . 
     Additional safety measures may be taken, such as providing bubble detectors in the fluid delivery path which stop operation immediately if bubbles are detected. Bubble detectors are well known in the art. 
     LIST OF REFERENCE SIGNS 
     
         
         P 1  first pump 
         P 2  second pump 
         V 1  first valve 
         V 2  second valve 
         a, b, c connections of first valve 
         d, e, f connection of second valve 
         A inlet of radiopharmaceutical 
         B, C, C′, C″ reference points 
         D start of metering section 
         E end of metering section 
         M 1 , M 2 , M 3  measurements 
         A 1 , A 2 , Ar, Am, Ac′, Ac″ activities 
           1  radiopharmaceutical 
           2  vial 
           3  shield 
           4  tubing 
           5  saline container 
           6  tubing 
           7  tubing 
           8 ,  8 ′ metering section 
           9  dose calibrator 
           10  tubing 
           11  injection needle 
           12  waste 
           13  controller 
           21 ,  22 ,  23  volumes of radiopharmaceutical 
           31  sliding element