Device for estimating the activity of a radioactive liquid

Abstract

Device (1) for measuring the activity of a radioactive liquid (2), comprising: a detection module (10), extending around a measurement chamber (3), intended to contain the liquid, and configured to detect ionizing radiation and to emit a detection signal; a processing unit (40), connected to the detection module, programmed to estimate an activity of the radioactive liquid from the detection signal; the device being characterized in that the detection module comprises: a solid scintillator detector (11), extending around the measurement chamber; at least two photodetectors (15), optically coupled to the scintillator detector; the device comprises a capillary (3), extending around a longitudinal axis (Δ), the capillary being arranged to be positioned for measurement, the capillary forming the measurement chamber.

Description

Title of the invention: Device for estimating the activity of a radioactive liquid Technical field

[0001] The technical field of the invention is the analysis of the volume or mass activity of a radioactive liquid, in particular with a view to use for diagnostic or medical treatment purposes. PREVIOUS ART

[0002] Some nuclear medicine applications require the introduction into the body of a product labeled with a radioactive isotope. This is also referred to as a radiopharmaceutical product. The product may have a medical treatment purpose, for example in the context of brachytherapy treatment. The product may also have a diagnostic purpose.

[0003] Among the radioactive isotopes, or radionuclides, usually used in nuclear medicine, we can cite for example HC, 18F, 67Ga, 90Y, 99mTc, H1In, 123I, 125I, 131I, 2O1T1. Prior to their injection into the body of a patient, it is necessary to quantify, as precisely as possible, their activity. It may also be useful to identify and quantify the presence of possible impurities resulting from the process of production of radioactive isotopes.

[0004] In a hospital environment, the activity of an isotope is quantified prior to its injection, using a measuring device usually called an activimeter. An activimeter is a detector, generally an ionization chamber, forming a well. The radioactive product is introduced, in liquid form, into the well and its activity is estimated. The radioactive product is contained in a container, such as a syringe or a bottle. The ionization chamber has previously been calibrated, making it possible to obtain a relationship between a current intensity, resulting from the ionization chamber, and the activity of the radioactive isotope. The calibration depends on the type of isotope used. The calibration also depends on the geometry of the measurement, that is to say the shape and nature of the container containing the radioactive product. The calibration is for example different when the radioactive product is contained in a syringe or a bottle.Calibration depends on the filling level as well as the isotope to be measured. Calibration generally requires the use of a specialized laboratory.

[0005] The inventors propose a device for estimating the volumetric, or mass, activity of a solution containing an isotope intended to be used in nuclear medicine, in a simple and automated manner, without requiring the use of calibration. complex. Statement of the invention

[0006] A first object of the invention is a device intended to measure the activity of radioactive liquid, and in particular of a drop of radioactive liquid, comprising: - a detection module, extending around a measuring chamber, intended to contain the liquid, the detection module being configured to detect ionizing radiation emitted in the measuring chamber and to emit a detection signal dependent on a quantity of radiation detected; - a processing unit, connected to the detection module, and programmed to estimate the activity of the radioactive liquid from the detection signal;

[0007] the device being characterized in that - the detection module includes: • a solid-state scintillator detector configured to produce scintillation photons when exposed to ionizing radiation, the scintillator detector extending around the measuring chamber; • at least two photodetectors, optically coupled to the scintillator detector, each photodetector being configured to detect scintillation photons and generate a detection signal dependent on the quantity of scintillation photons detected;

[0008] the device comprising a capillary, extending around a longitudinal axis, and delimiting an internal space intended to contain the radioactive liquid, the capillary being arranged to be placed in a measuring position, in which the scintillator detector extends around the internal space of the capillary, the capillary forming the measuring chamber.

[0009] Preferably, the scintillator detector extends around the capillary.

[0010] According to one possibility, the scintillator detector forms a wall of the capillary.

[0011] Advantageously, - an opening is made through the scintillator detector, along the longitudinal axis; - the capillary extends through the opening when arranged in the measuring position.

[0012] Each photodetector may in particular extend around a detection axis intersecting the longitudinal axis. The respective detection axes of each photodetector are preferably coplanar, and preferably in a plane perpendicular to the longitudinal axis. The respective detection axes of each photodetector are preferably regularly angularly spaced from each other, around the longitudinal axis.

[0013] The scintillator detector may comprise a spherical or cylindrical central portion lindrical or polyhedral through which the opening passes. The device is such that the capillary is inserted into the opening at least in the measuring position.

[0014] Each photodetector is preferably optically coupled to the scintillator detector by a planar face. The planar face is intended to promote optical coupling with the photodetector.

[0015] According to one possibility, the scintillator detector extends, from the opening, to at least one flat face, so that the scintillator detector comprises the central portion, around the opening, and the flat face.

[0016] Preferably, the scintillator detector comprises as many flat faces as there are photodetectors.

[0017] According to one possibility, the device comprises a material transparent to scintillation photons, extending between the scintillator detector and at least one flat face.

[0018] The device may comprise a spectrometric detector extending opposite the capillary, and connected to the processing unit. The spectrometric detector is connected to the processing unit, the processing unit being configured to detect the presence of impurities, in particular metallic impurities, in the liquid, from X-ray fluorescence peaks detected on a spectrum generated by the spectrometric detector.

[0019] Preferably, the device comprises a motorized translation unit, configured to move, in translation, the capillary, along the longitudinal axis, so that the capillary can pass between the measurement position, facing the scintillator detector, to at least one sampling position, the sampling position being offset, along the longitudinal axis, relative to the measurement position.

[0020] The device may comprise a pumping unit, configured to: - admit, in the sampling position, the liquid into the internal space of the capillary when the capillary is in contact with a solution contained in a reservoir, the liquid contained in the capillary constituting a sample of said solution; - and / or push back the liquid from the internal space of the capillary.

[0021] According to one possibility, the capillary comprises an internal face, delimiting the internal space, the internal face being hydrophobic.

[0022] According to a preferred embodiment, - the detection signal resulting from each photodetector comprises pulses, each pulse resulting from an interaction of a particle, forming the ionizing radiation, in the scintillator detector; - the processing unit comprises a coincidence detection circuit, configured to detect pulses detected in temporal coincidence by at least two photodetectors; - the processing unit is programmed to estimate the activity based on a quantity of pulses detected in temporal coincidence.

[0023] Preferably, the device comprises at least three photodetectors. The coincidence detection circuit is programmed to allow detection of pulses detected in temporal coincidences by two detectors, called double coincidences, and detection of pulses detected in temporal coincidences by three detectors, called triple coincidences. The processing unit can be programmed to estimate the activity as a function of a number of double coincidences detected per unit of time. The activity can be estimated from a detection efficiency, obtained by comparing a quantity of double coincidences with a quantity of triple coincidences detected over the same measurement period.

[0024] The device may comprise an observation camera, arranged to view the capillary when the capillary occupies an observation position, offset from the measurement position, the processing unit being programmed to estimate a volume of liquid in the capillary as a function of an image provided by the observation camera.

[0025] A second object of the invention is a method for estimating an activity of a liquid using a device according to the first object of the invention, comprising the following steps: a. introduction of a liquid sample into the capillary; b. arrangement of the capillary in the measuring position; c. acquisition of detection signals by each photodetector; d. based on the acquired detection signals, estimation of the activity of the liquid sample present in the capillary, using the processing unit.

[0026] According to one possibility, - during step a), the capillary occupies a sampling position, in contact with a reservoir containing the liquid; - between step a) and step b), the capillary is moved by the translation unit, from the sampling position to the measuring position.

[0027] According to one possibility, - the device comprises a pumping unit, as previously described; - during step a), the pumping unit is activated, so as to suck part of the liquid, present in the reservoir, towards the capillary.

[0028] Step d) may include: - detection, in the detection signals, of pulses emitted in temporal coincidence, by two photodetectors, called double coincidences; - taking into account a detection efficiency relative to double coincidences; - determination of the activity from a number of double coincidences detected per unit of time and the detection efficiency relative to the coincidences double incidences.

[0029] According to one possibility, - the device has three photodetectors - the detection efficiency relative to double coincidences is calculated from a ratio between • a number of pulses emitted, in the detection signals, in temporal coincidence, by three photodetectors, called triple coincidences; • the number of double coincidences.

[0030] Another object of the invention is a scintillator detector, crossed by a cylindrical opening, the cylindrical opening extending along a central axis, the scintillator detector comprising: - a central portion, formed of a solid material configured to generate scintillation photons under the effect of exposure to ionizing radiation, the central portion extending around the opening; - planar faces, optically coupled to the central portion, each planar face being configured to be coupled to a photodetector.

[0031] According to one possibility, the central portion is spherical, and extends around the cylindrical opening. According to another possibility, the central portion is cylindrical, and extends around the opening, around an axis coaxial with the central axis. According to another possibility, the central portion is polyhedral, for example cubic.

[0032] Preferably, the central portion has rotational symmetry about the central axis.

[0033] Preferably, the central portion extends, from the central axis, along a radius greater than 5 mm or 10 mm.

[0034] The invention will be better understood upon reading the description of the exemplary embodiments presented in the remainder of the description, in conjunction with the figures listed below. FIGURES

[0035] Figures 1A to 1C represent an example of a device according to the invention. In Figures 1A, 1B and 1C, a capillary of the device is respectively arranged in a sampling position, an observation position and a measurement position.

[0036] [Fig. 1D] shows a shutter and a bellows intended to ensure sealing of the measuring module with respect to ambient light.

[0037] [Fig.2A] shows an example of a scintillator detector.

[0038] [Fig.2B] represents the scintillator detector, described in connection with [Fig.2A], coupled with three photomultipliers.

[0039] [Fig.2C] shows another example of a scintillator detector.

[0040] [Fig.2D] shows another example of a scintillator detector.

[0041] Figures 3A and 3B show other possible configurations of the scintillator detector.

[0042] Figures 4A and 4B show a modeled scintillator detector geometry, in two different section planes.

[0043] Figures 5A and 5B are detection spectra, representing a probability of energy deposition by particles emitted by an activity of IBq of 18F and HC.

[0044] [Fig. 6A] shows an image of the sample, placed in the observation position.

[0045] [Fig.6B] shows an image of a graduated optical calibration object.

[0046] [Fig.6C] represents a processing of the image represented in [Fig.6B].

[0047] [Fig. 6D] shows an image of another sample, placed in the observation position.

[0048] [Fig.7] shows schematically the main steps of a method implementing the device according to the invention. PRESENTATION OF SPECIAL EMBODIMENTS

[0049] Figures 1A to 1C represent an embodiment of a device 1 according to the invention. The objective of the device is to quantify an activity of a small volume, typically a few pL, of a radiopharmaceutical solution comprising a radioactive isotope. The radioactive isotope is known. It may in particular be an isotope as described in the prior art.

[0050] Generally, the volume or mass activity of a solution, intended to be injected into the body of a patient, is very high. In order to obtain an activity measurement with good precision, it is preferable to use a sample of small volume, so as to avoid saturation of the detector used. The inventors consider that a volume of less than 10 pL, and preferably 1 pL or a few pL, is optimal. The volume can also be of the order of a few 100 nL or a few 10 nL or even of the order of nL. The volume activity is sufficiently high so that the total activity is easily measurable. Furthermore, the fact that the total activity of the sample is sufficiently high makes it possible to carry out measurements spaced out over time, and to verify that the decrease in activity as a function of time is consistent with the radioactive period of the isotope.

[0051] The radiopharmaceutical solution to be injected is contained, in liquid form, in a reservoir 20. An important element of the invention is the use of a capillary 3, intended to collect the sample 2 of the pharmaceutical solution. In the example shown, the capillary 3 is a quartz (fused silica) capillary, 15 cm long, with an internal diameter of 900 μm and an external diameter of 1200 μm. The capillary 3 extends around a longitudinal axis A. In this example, the longitudinal axis A is parallel to a vertical axis Z. The horizontal plane PXY is defined by two orthogonal axes X and Y.

[0052] The capillary 3 is movable in translation using a translation plate 4, preferably motorized. In the example shown, the translation plate is configured to move along a mast 5, parallel to the longitudinal axis A. The translation plate allows a translation, along the longitudinal axis A, of the capillary. The capillary can thus occupy different positions along the longitudinal axis, as described below.

[0053] The device 1 comprises a measurement module 10, intended to quantify the activity of the sample 2 previously taken from the capillary 3. The translation plate 4 is thus configured to move the capillary between: - a sampling position, in contact with the container 20, so as to take a sample 2 of radiopharmaceutical solution: the sampling position is shown in [Fig.lA]. The sample 2 is thus formed by a drop, or by several drops, resulting from the sampling. - an observation position, during which the sample 2 is placed facing an observation camera 30: the sampling position is shown in [Fig.IB], - a measuring position, during which the sample 2 is placed in the measuring module 10: the sampling position is shown in [Fig.lC].

[0054] The device is arranged so that when the capillary occupies the sampling position, the capillary is engaged in the reservoir 20, so as to be in contact with the radiopharmaceutical solution. The reservoir 20 is removable and may not be part of the device. It may be a simple bottle. The capillary 3 is connected, by a fluid connection, to a pumping unit 21. In this example, the capillary plunges into the reservoir 20 by a first end 3b. The capillary has a second end 32 opposite the first end 31. The second end 32 is connected, by a steel tube 22, to the pumping unit 21. In this example, the pumping unit 21 is a syringe connected to a syringe pump. The steel tube 22 (internal diameter 2 mm), acts as a fluid connection between the capillary 3 and the pumping unit 21.Under the effect of the actuation of the syringe pump, the pumping unit allows the application of a depression or an overpressure in the capillary. This allows pumping or delivery of the radiopharmaceutical solution through the first end 3i of the capillary. A liquid sample 2 is thus taken. The admission of the liquid sample 2 into the capillary 3 has been represented in [Fig.lA] by an arrow.

[0055] The device may comprise a tracking camera 23, configured to visualize the admission of the liquid sample into the capillary 3. The tracking camera 23 is arranged to make it possible to visualize the position of the capillary 3 relative to the solution present in the reservoir 20. When the first end 3i plunges into the solution, the pumping unit 21 can be operated. The device 1 may comprise a scale 24, supporting the tank 20.

[0056] Following the collection of sample 2, capillary 3 is translated by translation unit 4, so as to move away from reservoir 20. Pumping unit 21 can be actuated, so as to move sample 2 inside capillary 3.

[0057] The capillary 3 is then moved, parallel to the longitudinal axis A, to an observation position, facing an observation camera 30. The observation camera makes it possible to form an image of the capillary 3, so as to estimate the volume of the sample 2. The calculation of the volume of the sample is described subsequently, in connection with FIGS. 6A to 6D. A light source 31 is arranged so that when the capillary occupies the observation position, the sample 2 taken extends between the observation camera 30 and the light source 31. It is understood that for a usable image of the sample to be obtained, the capillary is transparent.

[0058] Following the acquisition of the image of the sample 2 by the observation camera 30, the capillary 3 is translated, by the translation stage 4, to a measurement position. In the measurement position, the sample 2 is placed in the measurement module 10. The device comprises a processing unit 40, connected to the measurement module 10, programmed to estimate an activity of the sample 2 from detection signals from the measurement module 10.

[0059] Thus, unlike the prior art, the capillary delimits an internal space, which contains the sample 2 whose activity is measured. The capillary thus forms a measuring chamber.

[0060] The measurement module 10 comprises the instrumentation allowing an estimation of the activity of the sample. The implementation of the measurement module assumes that the radioactive isotope contained in the sample is known.

[0061] Figures 2A and 2B schematically represent a scintillator detector 11 whose layout is particularly suitable for the intended application. [Fig.2A] is a three-dimensional view, while [Fig.2B] is a sectional view, in a plane perpendicular to the central axis, passing through the center of the scintillator detector. The scintillator detector 11 is formed from a solid material configured to generate scintillation photons when exposed to particles forming ionizing radiation. These may in particular be charged particles, such as [3 or [3+, or X or y photons. The scintillation material may be an organic polymer, to which fluorescent dopants have been added. It may also be an inorganic scintillator, for example YaG(Ce), NaI, CsI, LaBr3, BGO (Bismuth Germanate).The use of an inorganic scintillator increases the sensitivity of the measurement because the stopping power of this type of scintillator is greater than the stopping power of organic scintillators. In addition, inorganic scintillators contain atoms with the number . atomic is superior to organic compounds. This promotes photoelectric interactions, during which photons release all their energy into the scintillator material in a single interaction.

[0062] Despite their lower sensitivity compared to inorganic scintillators, a significant advantage of organic scintillator materials is the ease of shaping, which can be achieved by molding. Figures 2A to 2D show different configurations of an organic scintillator detector, based on vinyl-toluene, which can be obtained by molding.

[0063] The scintillator detector 11 is optically coupled to several photodetectors 15. The latter may in particular be photomultipliers, for example of the Hamamatsu H13175U-110 type. Preferably, the scintillator detector 11 comprises or is optically coupled to flat faces 12, each photodetector 15 being applied against a flat face 12, possibly using a coupling fluid. According to one possibility, at least one photodetector, or even each photodetector, is or comprises a photodiode. It may for example be a SiPM (Si photomultiplier - Silicon Photomultiplier) type photodetector.

[0064] An important aspect of the scintillator detector is that it is crossed by an opening 13, extending around a central axis A'. When using the scintillator detector in the device 1, the central axis A' coincides with the longitudinal axis A. The opening 13 is sized to allow translation of the capillary 3 through the scintillator detector 11. For example, when the external diameter of the capillary 3 is 1.2 mm, the diameter of the opening 13 may be equal to 1.4 mm. Generally speaking, the diameter of the opening is preferably between 1 mm and 1 cm.

[0065] The scintillator detector may have a parallelepiped shape, with four flat faces parallel to the central axis A'. Such a possibility is shown diagrammatically in [Fig.3A]. It may also have a polyhedral shape, with flat faces parallel to the central axis A'

[0066] Preferably, the scintillator detector has rotational symmetry about the central axis A'. In the example shown in Figures 2A and 2B, the scintillator detector comprises a central portion 11', of spherical shape, extending around the opening 13. The spherical portion 11' is arranged around the opening 13, and preferably symmetrically around the central axis A'. The fact that the scintillator material has a spherical portion, around the opening 13, is considered advantageous for reasons of symmetry, in particular during the processing of detection signals described below.

[0067] According to one possibility, the scintillator detector 11 may comprise a cylindrical central portion, extending around the central axis A'. Such a possibility is shown in [Fig.3B]. The wall of the capillary may be formed from a scintillator material.

[0068] When the central portion 11' is a sphere or a cylinder, its radius may be between 15 mm and 25 mm when the scintillator material is an organic scintillator. The radius is for example equal to 18 mm. The optimal dimensions vary depending on the type of scintillator material used. It is considered optimal for the central portion 11' to be spherical.

[0069] In order to facilitate coupling with the photodetectors 15, the scintillator detector 11 comprises flat faces 12, and preferably parallel to the central axis A'. In FIGS. 2A and 2B, the scintillator is a single piece. It comprises cylindrical coupling portions 14, each coupling portion 14 extending between the central portion 11' and a flat face 12. Each flat face 12 extends perpendicular to a detection axis, which is secant, and preferably perpendicular, to the central axis A'. In [Fig.2B], three different detection axes ôb ô2 and ô3 are shown, perpendicular to which three different flat faces 12 extend. Preferably, the detection axes are distributed according to a symmetry around the central axis A'. Preferably, the detection axes are coplanar. The plane along which the detection axes extend is preferably perpendicular to the central axis A'. In the example of [Fig.2B], the adjacent detection axes are angularly offset by the same angle 0 equal to 120°. According to other possibilities, the scintillator comprises two planar faces, perpendicular to a detection axis, which corresponds to an angular offset of 180°. According to another possibility, the scintillator comprises four planar faces, such that the detection axes of two adjacent planar faces are angularly offset by 90°. More generally, the scintillator 11 may comprise n planar faces 12, arranged so that the respective detection axes of two adjacent planar faces are offset by an angle 0 equal to 360° / n.

[0070] In the example of Figures 2A and 2B, the scintillator 11 is a single piece: the central portion 11' and each coupling portion 14 are formed from the same scintillator material. Such a configuration can be obtained by molding when the scintillator material is organic. In the example of [Fig.2C] the central portion 11' is formed from a scintillator material, while each coupling portion 14 is formed from a material transparent to scintillation photons. Each coupling portion 14 is attached to the central portion 11'. [Fig.2C] is a view in a section plane passing through each detection axis.

[0071] [Fig.2D] is also a view in a section plane passing through each detection axis. In [Fig.2D], the central portion 11' is truncated, so as to form the flat faces 12. In this configuration, there is no coupling portion 14.

[0072] The measurement module 10 may comprise a spectrometric detector 17. In [Fig.2B], a spectrometric detector 17 is shown, arranged opposite the scintillator detector 11. The spectrometric detector is configured to detect X or gamma photons emanating from the scintillator 11. It is connected to a spectrometry circuit 17', configured to form an energy spectrum. More precisely, each time a photon is detected by the spectrometric detector, the latter generates a pulse whose amplitude is correlated to the energy deposited by the photon in the spectrometric detector. The spectrometry circuit 17' allows the formation of a spectrum, which corresponds to a histogram of the amplitudes of the pulses resulting from the spectrometric detector 17. The spectrum corresponds to a number of pulses detected, during an acquisition period, for different energy channels.

[0073] The spectrometry circuit is connected to the processing unit 40. More precisely, the processing unit implements a spectral analysis algorithm, allowing the identification of certain singularities. These may for example be peaks resulting from the X-ray fluorescence of certain materials, in particular metallic materials, for example Fe, In or Pd. Metallic materials, resulting from the process of production of the radioactive isotope, form impurities in the radiopharmaceutical solution. The excitation, inducing the X-ray fluorescence, may come from X-rays or gamma rays emitted directly or indirectly by the isotope. For example, when the isotope is a [3+ emitter, the fluorescence may be induced by the irradiation of the sample by photons resulting from the annihilation of the [3+ particle.

[0074] The spectrometric detector may use a detection material of the CeBr3 or NaI(Tl) or CsI or CdTe type. This type of material makes it possible to form a spectrum of acceptable quality using a spectrometric detector that is sufficiently compact to be integrated into the detection module 10. The spectrometric detector may be of the GeHP type, provided that an adequate cooling means is available, for example a cryogenic tank or thermoelectric cooling.

[0075] The detection module 10 extends, along the longitudinal axis A, between a lower face 10inf and an upper face 10sup. Given the presence of the photodetectors 15, which may be sensitive to visible light, the detection module 10 is made sealed by using a shutter 18, on the lower face 10inf facing the container 20, and by an opaque bellows 19, extending around the capillary, from the upper face 10sup. [Fig.lD] shows schematically the arrangement of the shutter 18 and the bellows 19 on the detection module. When the capillary 3 is in the measuring position, the shutter is closed. The opening of the shutter allows a translation of the capillary so that the sample 2 is outside the measuring module, for example in the observation position or in the sampling position. The opaque bellows is configured to fold or refold depending on the translation of the capillary 3.

[0076] The inventors established a numerical model in order to simulate the performance of detection of a scintillator detector as described in connection with Figures 2A and 2B. [Fig.4A] shows a sectional view of the digital model, in an XZ plane, passing through the central axis. [Fig.4B] shows a sectional view of the digital model, in an XY plane, perpendicular to the central axis, and passing through the center of the spherical portion 11'.

[0077] Such a numerical model is intended to estimate the energy absorbed by the scintillator detector when the latter is subjected to exposure to radiation produced by a predetermined isotope. In [Fig.5A], for a disintegration of [3+ of 18F, a probability density of releasing, in the scintillator detector, different energy values ​​is represented. The abscissa axis corresponds to the energy, expressed in keV. The ordinate axis represents, at each disintegration, a probability of depositing, in the scintillator detector, the energy corresponding to the abscissa axis. In [Fig.5A], curve a) corresponds to the energy deposited by a positron emitted by 18 F, without taking into account the annihilation. Curve b) corresponds to the energy deposited by the two gamma photons of energy 511 keV resulting from the annihilation of the positron.Curve c) corresponds to an energy deposition probability combining the positron path in the scintillator detector as well as annihilation, giving rise to the emission of 511 keV photons. Curve d) corresponds to curve c) taking into account a branching factor of 97% of the decay [3+ for 18F.

[0078] [Fig.5B] is a figure similar to [Fig.5A], established by considering the decay [3+ of 1 IC, the branching rate being 99%.

[0079] In Figures 5A and 5B, the low energy emissions due to electron capture do not pass through either sample 2 or capillary 3. They do not release any energy in scintillator detector 11.

[0080] In Figures 5A and 5B, the sample is a drop of physiological liquid having a unit activity of 1 Bq of 18F and HC respectively.

[0081] Curves d) of Figures 5A and 5B correspond to absorption spectra of the scintillator detector, respectively for an activity of IBq of 18F and HC. These absorption spectra can be used as input data for the determination of the activity of a sample 2, as described below.

[0082] When implementing the device 1, the processing unit 40 is connected to each photodetector 15, and collects a detection signal generated by each of them. More precisely, each photodetector is connected to a coincidence detection circuit 16, intended to determine the pulses detected in temporal coincidence by two photodetectors (double coincidences) as well as by the three photodetectors (triple coincidences). As described in the publication Broda R. et al “Radionuclide metrology using liquid scintillation counting”, Metrologia 44 (2007), when using a sample, considered as a pure [3 emitter, of unknown activity, it can be shown that a detection efficiency q, called absolute detection efficiency, can be determined from a ratio between the number of triple coincidences to the number of double coincidences.

[0083] More precisely, if NT corresponds to the number of triple coincidences and ND corresponds to the number of double coincidences, the ratio El, designated RCTD (Ratio of ;VD triple coincidences on doubles), is such that:

[0084] RCTD-

[0085] with

[0086] fi Y) — IJ — clx

[0087] where: - $Œ} is the absorption spectrum of the isotope considered, which corresponds to the curves d) of figures 5A (for 18F) and figures 5B (for HC); - v is the quantum efficiency of the photomultipliers, which is not known; - % is a luminous efficiency of the scintillator material, which corresponds to a number of scintillation photons emitted per unit of absorbed energy (photons.keV '); - is the linear energy loss of an incident particle (|3+ or [3 ) in the dx scintillator detector; - Emax is the maximum energy of the emission spectrum of the incident particle; - kB is a semi-empirical parameter, usually called the Birks parameter, expressed in cm. MeV1. This parameter describes the nonlinearity of the scintillator. It is usually between 0.007 and 0.015 cm. MeV1.

[0088] The parameters S(E).ct are input data. RCTD is data measured, resulting from the coincidence detection circuit 16. We can determine the product vz?o, product of the quantum efficiency of the photomultipliers by the luminous efficiency of the scintillator material, so as to obtain the absolute detection efficiency The calculated yield is the one that allows us to verify equality (1).

[0089] The calculated efficiency is used to determine a detection efficiency eD of double coincidences, according to the expression:

[0090] Rd - (3(1 _grf _2(1 -erf ) <3)

[0091] The Ad activity of the isotope is then determined, from Navec:

[0092] Act=

[0093] ND corresponds to a so-called logical sum of the double coincidences detected per unit of time. For example, if we have three photodetectors 15i, 152 and 153, Apest such that:

[0094] Nd= N^2 + NU3 + N2.3-2Nw (5)

[0095] where jVf 2, N and A / 2.3 are the number of double coincidences detected, per unit of time, by the photodetectors 15i and 152, 15i and 153152 and 153 respectively. corresponds to the number of triple coincidences detected per unit of time: N y 23 = Nt (6). The processing unit 40 receives the quantities Nï 2, N1 3 and N23 and Nt of the coincidence circuit 16. It can then determine 7 by implementing expression (1). This makes it possible to obtain £d by implementing (3), from 7, then the activity Ad by expression (4).

[0096] Preferably, the efficiency is determined during each measurement, by a ratio between the number of triple coincidences to the number of double coincidences. The efficiency of detection of double coincidences £d can thus be determined, according to (3), during each measurement. This avoids the need for calibration carried out in the laboratory, which is a notable advantage of the invention.

[0097] The activity Ad of sample 2 can be estimated at different successive measurement times 1, so as to obtain values ​​Active). The evolution of Active) as a function of time can be compared with a theoretical evolution, established from the decay period of the isotope considered. A difference between the measured evolution and the theoretical evolution can mean the presence of pollution in sample 2.

[0098] The activity (Active) of the sample 2, measured at the measurement time, is preferably normalized by the volume of the sample. This allows an estimation of the volume or mass activity of the radiopharmaceutical solution present in the container 20.

[0099] The volume of the sample can be estimated using an image acquired by the observation camera 30, while the sample 2 occupies the observation position. Given the geometry of the capillary, without any particular treatment, the sample extends between two menisci, as shown in FIG. 6A. The processing unit 40 receives the image acquired by the observation camera, and can estimate a volume V of the sample, for example by applying the expression:

[0100] + (7)

[0101] where:

[0102] - L is the total length of the sample;

[0103] -1 is the internal radius of the capillary;

[0104] - H} is a height of the first meniscus;

[0105] - H2 is a height of the second meniscus.

[0106] The quantities L,? and H2 are estimated from the image. The observation camera has previously been calibrated, for example by the acquisition of an image of a target or a graduated ruler. [Fig.6B] shows an image from an Olympus OB-M object micrometer. In [Fig.6C], an intensity profile of an acquired image is shown, each peak corresponding to a graduation. In [Fig.6C], the ordinate axis corresponds to an intensity and the abscissa axis corresponds to pixels aligned according to the light line shown in [Fig.6B]. Since the distance between each graduation is known, a dimension seen by each pixel of the observation camera can be estimated. It is estimated that the performance of the observation camera allows a volume of 1 pL to be estimated with an uncertainty of less than 1%.

[0107] According to one possibility, the internal wall of the capillary is hydrophobic, or has been subjected to a hydrophobic treatment. Such a treatment makes it possible to reduce, or even eliminate, the presence of menisci on either side of the sample. [Fig.6D] is an image of a sample 2 in a capillary whose internal face has previously been subjected to a hydrophobic treatment. It is understood that the estimation of the volume of the sample, from the observation image, is simpler, because the geometry of the sample corresponds to a cylinder.

[0108] After the activity of the sample has been determined, the capillary is translated to the sampling position and the sample can be forced back into the reservoir 20 by applying an overpressure in the capillary.

[0109] [Fig.7] shows the main steps of a method of implementing a device as previously described.

[0110] During a step 100, the capillary is moved into the sampling position and a sample 2 is taken under the effect of the pumping unit.

[0111] During a step 110, the capillary is placed in the observation position and an image of the sample is acquired by the observation camera, which makes it possible to estimate the volume (or mass) of the sample.

[0112] During a step 120, the capillary is placed in the measurement position, in the measurement module 10. The activity of the sample is estimated from the detection signals resulting from each photodetector, and from the number of double coincidence detections detected. Step 120 can be implemented before step 110.

[0113] The inventors used a device as previously described, the scintillator detector being like that described in connection with Figures 2A and 2B. After each measurement, each sample was ejected into a liquid scintillation solution, so as to obtain a reference measurement. The isotope was 18F or nC. Table 1 summarizes the experimental results obtained. Reference test Isotope Activity volume (Bq / mL) Activity volume - reference method Deviation (%) (Bq / mL) 1 18p 7.93 107 8.23 ​​107 3.7% 2 18p 7.52 107 7.52 107 0.01% 3 HC 9.54 106 9.47 106 0.61%

[0114] Table 1

[0115] In Table 1, the third and fourth columns correspond respectively to the volume activity determined by implementing the invention and the reference method. In Test 1, a capillary without hydrophobic treatment was used. In Test 2, the capillary had been subjected to a hydrophobic treatment, which may explain the smaller difference between the implementation of the invention and the reference method.

[0116] The device which is the subject of the invention makes it possible to estimate the activity of a radioactive liquid without requiring complex calibration, involving a reference laboratory. Indeed, the measurement is carried out on a small volume sample, taken from a radiopharmaceutical solution. The activity is estimated on the basis of double coincidence measurements, as previously described, the detection efficiency being able to be calculated by a ratio of triple coincidences to double coincidences.

[0117] The device that is the subject of the invention is easily automated, which makes it possible to limit the intervention of operators near the radioactive liquid. Indeed, the translation of the capillary, the control of the pumping unit and that of the measuring module can be automated. This contributes to reducing the dosimetry of the personnel involved.

Claims

1.

2.

3. Claims Device (1) intended to measure the activity of a radioactive liquid (2), comprising: - a detection module (10), extending around a measuring chamber (3), intended to contain the liquid, the detection module being configured to detect ionizing radiation emitted in the measuring chamber and to emit a detection signal dependent on a quantity of radiation detected; - a processing unit (40), connected to the detection module, and programmed to estimate an activity of the radioactive liquid from the detection signal; the device being characterized in that - the detection module includes: • a solid scintillator detector (11) configured to produce scintillation photons when exposed to ionizing radiation, the scintillator detector extending around the measuring chamber; • at least two photodetectors (15), optically coupled to the scintillator detector, each photodetector being configured to detect scintillation photons and generate a detection signal dependent on the quantity of scintillation photons detected; - the device comprises a capillary (3), extending around a longitudinal axis (A), and delimiting an internal space intended to contain the radioactive liquid, the capillary being arranged to be placed in a measuring position, in which the scintillator detector extends around the internal space of the capillary, the capillary forming the measuring chamber. The device of claim 1, wherein the scintillator detector extends around the capillary. A device according to any preceding claim, wherein the scintillator detector forms a wall of the capillary.

4. Device according to any one of the preceding claims, in which: - an opening (13) is made through the scintillator detector (11), along the longitudinal axis (A); - the capillary extends through the opening when it is arranged in the measuring position.

5. Device according to any one of the preceding claims, in which each photodetector extends around a detection axis (ôb ô 2, ô3), secant from the longitudinal axis.

6. A device according to claim 5, wherein the respective detection axes of each photodetector are coplanar.

7. Device according to any one of claims 5 or 6 in which the respective detection axes (ôb ô2, ô3) of each photodetector (15) are regularly angularly spaced from each other, around the longitudinal axis.

8. Device according to any one of claims 4 to 7, in which the scintillator detector (11) comprises a spherical or cylindrical or polyhedral central portion (11'), crossed by the opening (13).

9. A device according to any preceding claim, wherein each photodetector (15) is optically coupled to the scintillator detector (11) by a planar face (12).

10. Device according to claim 9 and claim 8, in which the scintillator detector extends, from the opening, to at least one flat face (12), so that the scintillator detector comprises the central portion (11'), around the opening, and at least one flat face.

11. Device according to claim 10, in which the scintillator detector (11) comprises as many flat faces (12) as there are photodetectors.

12. Device according to claim 9, comprising a material transparent to scintillation photons, extending between the scintillator detector and at least one planar face.

13. Device according to any one of the preceding claims, comprising a spectrometric detector (17), extending opposite the capillary, and connected to the processing unit (40).

14. Device according to any one of the preceding claims, comprising a motorized translation unit (4), configured to move, in translation, the capillary, along the longitudinal axis, so as to that the capillary can pass between the measuring position, facing the scintillator detector, to at least one sampling position, the sampling position being offset, along the longitudinal axis, relative to the measuring position.

15. Device according to claim 14, comprising a pumping unit (21), configured to: - admit, in the sampling position, the liquid into the internal space of the capillary when the capillary is in contact with a solution contained in a reservoir, the liquid contained in the capillary constituting a sample of said solution; - and / or discharge the liquid from the internal space of the capillary.

16. Device according to any one of the preceding claims, in which the capillary comprises an internal face, delimiting the internal space, the internal face being hydrophobic.

17. Device according to any one of the preceding claims, wherein - the detection signal resulting from each photodetector comprises pulses, each pulse resulting from an interaction of a particle, forming the ionizing radiation, in the scintillator detector; - the processing unit comprises a coincidence detection circuit (16), configured to detect pulses detected in temporal coincidence by at least two photodetectors; - the processing unit (40) is programmed to estimate the activity as a function of a quantity of pulses detected in temporal coincidence.

18. Device according to any one of the preceding claims, comprising an observation camera (30), arranged to view the capillary when the capillary occupies an observation position, offset from the measurement position, the processing unit being programmed to estimate a volume of liquid in the capillary as a function of an image provided by the observation camera.

19. Method for estimating an activity of a liquid using a device according to any one of the preceding claims, comprising the following steps: a. introduction of a liquid sample (2) into the capillary (3); b. arrangement of the capillary in the measurement position; c. acquisition of detection signals by each photodetector (15); d. as a function of the acquired detection signals, estimation of the activity of the liquid sample, present in the capillary, using the processing unit.

20. Method according to claim 19, in which the device is a device according to claim 14, and in which: - during step a), the capillary occupies a sampling position, in contact with a reservoir comprising the liquid; - between step a) and step b), the capillary is moved by the translation unit from the sampling position to the measurement position.

21. Method according to claim 20, in which - the device is a device according to claim 15; - during step a), the pumping unit is activated, so as to suck a part of the liquid, present in the reservoir, towards the capillary.

22. Method according to any one of claims 19 to 21, in which step d) comprises: - detection, in the detection signals, of pulses emitted in temporal coincidence, by two photodetectors, called double coincidences; - taking into account a detection efficiency relative to the double coincidences (eD); - determination of the activity from a number of double coincidences detected per unit of time and the detection efficiency relative to the double coincidences.

23. The method of claim 22, wherein - the device has three photodetectors - the detection efficiency relative to double coincidences is calculated from a ratio between • a number of pulses emitted, in the detection signals, in temporal coincidence, by three photodetectors, called triple coincidences; • the number of double coincidences.

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