U.S. patent application number 17/582345 was filed with the patent office on 2022-05-12 for accelerator-driven neutron activator for brachytherapy.
The applicant listed for this patent is ADVANCED ACCELERATOR APPLICATIONS. Invention is credited to Stefano BUONO, Luca MACIOCCO.
Application Number | 20220148753 17/582345 |
Document ID | / |
Family ID | |
Filed Date | 2022-05-12 |
United States Patent
Application |
20220148753 |
Kind Code |
A1 |
MACIOCCO; Luca ; et
al. |
May 12, 2022 |
ACCELERATOR-DRIVEN NEUTRON ACTIVATOR FOR BRACHYTHERAPY
Abstract
A neutron activator for neutron activation of a material, the
neutron activator being configured to produce neutrons from an
interaction with a proton beam (7), the neutron activator
comprising: a neutron source comprising a metallic target (1), and
a Beryllium first reflector-moderator (4) peripheral to the neutron
source and comprising a neutron activation-area (10) configured to
accommodate the neutron source and the material to be activated,
the neutron activation area (10) of the first reflector-moderator
(4) comprising a bore configured to accommodate the neutron
source.
Inventors: |
MACIOCCO; Luca; (Crozet,
FR) ; BUONO; Stefano; (New York, NY) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
ADVANCED ACCELERATOR APPLICATIONS |
Saint Genis Pouilly |
|
FR |
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Appl. No.: |
17/582345 |
Filed: |
January 24, 2022 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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16605543 |
Oct 16, 2019 |
11257603 |
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PCT/EP2018/060416 |
Apr 24, 2018 |
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17582345 |
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International
Class: |
G21G 1/06 20060101
G21G001/06 |
Foreign Application Data
Date |
Code |
Application Number |
Apr 24, 2017 |
EP |
17305461.0 |
Claims
1. A neutron activator for neutron activation of a material, the
neutron activator being configured to produce neutrons from an
interaction with a proton beam emitted along a beam axis, the
proton beam having an energy comprised between 16 MeV and 100 MeVr
and a beam intensity up to 1 mA, the neutron activator comprising:
a neutron source comprising a metallic target presenting a
longitudinal axis intended to be arranged parallel to the beam
axis, wherein the metallic target has a hollow conical shape, the
longitudinal axis of said conical shape being aligned with the
proton beam, and a Beryllium first reflector-moderator peripheral
to the neutron source and comprising a neutron activation area
configured to accommodate the neutron source and the material to be
activated, the neutron activation area of the first
reflector-moderator comprising a bore extending along a bore axis
and configured to accommodate the neutron source so that the bore
axis and the longitudinal axis are coaxial.
2. The neutron activator according to claim 1, wherein the neutron
activation area of the first reflector-moderator further includes
at least one activation channel extending along a channel axis
parallel to the bore axis at the vicinity of the bore, the
activation channel being configured to load the material to be
activated.
3. The neutron activator according to claim 2, wherein the neutron
activation area comprises a plurality of activation channels
distributed, around the bore.
4. The neutron activator of claim 1, further comprising a cooling
area in direct contact with an outer surface of the target (1) for
receiving a flow of fluid for cooling the target (1) during neutron
generation.
5. The neutron activator according to claim 1, wherein the aperture
of the hollow conical target and the thickness of its lateral walls
are optimized so that (i) part of the protons received from the
proton beam have sufficient energy to release the fraction of the
thermal energy corresponding to the Bragg peak outside the metallic
target, (ii) the power density inside the target is reduced to at
least 50% as compared to the power density in a target where all
the protons received from the proton beam release their thermal
energy inside the target, and, (iii) the number of generated
neutrons in the target is at least 70% equal to the number of
neutrons generated in a target having a thickness where all the
protons received from the proton beam release their thermal energy
inside the target.
6. The neutron activator according to claim 1, wherein the aperture
of the hollow conical target and the thickness of its lateral walls
is optimized so that (i) the protons received from the proton beam
lose all their energy within the metallic target, and (ii) the
stresses generated by the temperature gradients in the target
remain within the elastic limit of the metallic target, while still
keeping the cooling liquid temperature below the boiling point.
7. The neutron activator according to claim 4, further comprising,
housed in the first reflector-moderator: an inlet channel conveying
the cooling fluid to a flow guide, a flow guide delimiting the
cooling area for guiding the cooling fluid along the outer surface
of the target as a flow from the inlet channel to the outlet
channel, an outlet channel for removing the cooling fluid from the
flow guide.
8. The neutron activator according to claim 7, wherein the flow
guide is at least partly conical so that said conical flow guide
covers the outer surface of the conical target thereby delimiting a
cooling area surrounding the outer surface of the conical
target.
9. The neutron activator according to claim 1, wherein an aperture
of the conical target is comprised between 20.degree. and
45.degree..
10. The neutron activator according to claim 1, wherein the
metallic target is made of Beryllium or Tantalum.
11. The neutron activator according to claim 1, wherein said first
reflector-moderator is cylindrical along the bore axis.
12. The neutron activator according to claim 1, presenting an
overall dimension that does not exceed a volume of a cube of 1
meter side.
13. The neutron activator according to claim 1, further comprising
a second reflector-moderator embedding said first
reflector-moderator (4).
14. A neutron activation system for neutron activation of a
material, comprising: a generator configured to produce a proton
beam along a beam axis, the proton beam having an energy comprised
between 16 MeV and 100 MeV, and a beam intensity up to 1 mA, a
neutron activator according to claim 1 arranged so that the
longitudinal axis of the target is parallel to the beam axis.
15. The neutron activation system according to claim 14, wherein
the neutron activation area of the first reflector-moderator
further includes at least one activation channel extending along a
channel axis parallel to the bore axis at the vicinity of the bore,
the activation channel being configured to load the material to be
activated, and further comprising a supplying device for loading
the material to be activated, the supplying device being connected
to the activation channel and configured to move samples of
material to be activated along the activation channel.
16. Use of the neutron activation system of claim 14 for producing
.beta..sup.- emitting radioisotope suitable for Nuclear Medicine
applications.
17. A method for neutron activation of a material, said method
comprising: a) providing the material to be activated, b) placing
the material at the activation area of the neutron activator as
defined in claim 1, c) generating a proton beam at an energy
suitable for neutron activation of said material, and having for
example an intensity up to 1 mA thereby activating said
material.
18. The method of claim 17, wherein the target is cooled by a flow
of cooling liquid at a static pressure comprised between 1 and 20
bar and reaching velocity comprised between 8 m/s and 24 m/s at the
target surface.
19. The method of claim 17, wherein said material to be activated
is contained within or in the form of a microparticle or
nanoparticle.
20. The neutron activator according to claim 12, wherein the
overall dimension that does not exceed the volume of a cube of 0.75
meter side.
21. The neutron activator according to claim 12, wherein the
overall dimension that does not exceed the volume of a cube of 0.50
meter side.
22. The neutron activation system according to claim 14, wherein
the generator is configured to produce the proton beam having an
energy comprised between 30 MeV and 70 MeV.
23. The neutron activation system according to claim 14, wherein
the generator is configured to produce the proton beam having a
beam intensity up to 350 .mu.A for 70 MeV.
24. The neutron activation system according to claim 14, wherein
the generator is configured to produce the proton beam having a
beam intensity up to 1 mA for 30 MeV.
25. Use according to claim 16 for producing .sup.166Ho, .sup.186Re,
.sup.188Re, .sup.177Lu, .sup.198Au, .sup.90Y, .sup.227Ra and
.sup.161Tb.
26. The method of claim 18, wherein the cooling liquid is
water.
27. The method of claim 17, wherein the proton beam has an energy
between 16 MeV and 100 MeV.
28. The method of claim 17, wherein the proton beam has an energy
between 30 MeV and 70 MeV.
29. The method of claim 17, wherein the proton beam has an
intensity up to 350 .mu.A for 70 MeV.
30. The method of claim 17, wherein the proton beam has an
intensity up to 1 mA for 30 MeV.
31. The neutron activator according to claim 3, wherein the
activation channels are equally distributed around the bore.
32. The method of claim 19, wherein said material is in the form of
Holmium-oxide microparticles or nanoparticles.
Description
TECHNICAL FIELD
[0001] The field of the invention is that of activation of doses of
injectable suspensions of particles through the production of a
suitable neutron field.
[0002] The invention particularly relates to a neutron activator
for production of radioisotopes of interest, which operating
principle is based on the interaction of a proton beam with a solid
target, which generates neutrons that are then moderated/reflected
in a solid assembly to obtain a favourable neutron spectrum for the
(n, .gamma.) reactions in the isotopes of interest (for example
.sup.165Ho, and .sup.176Lu).
BACKGROUND ART
[0003] Treatment of cancer tumours is based on three main
therapeutic classes (frequently combined for increasing the chances
of recovery): surgery, chemotherapy and external radiotherapy.
[0004] Brachytherapy or "in situ" radiotherapy is often recommended
in addition to surgery or chemotherapy (as in breast or cervical
tumors), or in alternative, constituting then the exclusive
first-line treatment (as in prostate cancer in US, treatment of
hepatocarcinomas, or other hepatic tumors).
[0005] Rapidly dividing cells are particularly sensitive to damage
by radiation. For this reason, some cancerous growths can be
controlled or eliminated by administering or planting a small
radiation source, usually a gamma or beta emitter, in the target
area.
[0006] The main advantage of brachytherapy procedures it that they
give less overall radiation to the body, minimising the exposure of
healthy tissues, are more localized to the target tumor and are
cost-effective.
[0007] .beta.'-emitting radioisotopes can be produced through
neutron irradiation of the corresponding stable isotopes.
[0008] Currently such isotopes are produced only in research
nuclear reactors, but the main disadvantages rely on the low
availability of reactors in Europe for medical use, combined with
tight schedule and ageing problems.
[0009] Consequently, a need still exists for alternative methods
for the efficient production of neutron-activated radioisotopes
using cyclotrons for medical applications.
[0010] One of the objects of the present disclosure is to propose
an alternative to the production of radioisotopes for medical use,
in nuclear reactors.
[0011] Another object is to improve the efficiency of the method of
production of radioisotopes for medical use.
[0012] Another object of the invention is to provide a device and a
method for neutron activation of a material, for producing
radioisotopes.
[0013] WO 98/59347 discloses that a material exposed to a neutron
flux by distributing it in a neutron-diffusing medium surrounding a
neutron source can be used to produce useful radio-isotopes, in
particular for medical applications, from the transmutation of
readily-available isotopes included in the exposed material. The
neutron source consists of a beryllium or lithium target bombarded
with a charged particle beam.
[0014] A major drawback of this method is that the dimensions of
the activator are very big in order to contain the neutrons within
the system during their elastic-scattering path in the material.
This also results in a relevant dilution of the neutron flux, in
particular at lower energies (so after several scattering
interactions).
[0015] WO 2016/037656 discloses a method and an activator that
enhances captures in the resonance region. The strength of the flux
of neutrons is optimized by reflectors and/or moderators.
[0016] With respect to WO 98/59347, it proposes some general
approaches aiming at reducing the activator size while exploiting
the neutron-elastic-scattering properties of lead, and therefore
the Adiabatic Resonance Crossing principle in the activation area.
This approach has been numerically and experimentally analysed in
2005-2009 by the inventors with the experimental validation of an
activator with a lead core and a graphite reflector. The results of
such research led to the conclusion that the most efficient
approach to activate the considered isotopes was not to use the
peculiar properties of lead (transparency and elastic scattering)
but focusing on an efficient moderation-reflection, which provides
the solution of the present invention. Furthermore, in preferred
embodiment of the invention, the optimal position of the samples is
as close as possible to the proton target rather than in specific
positions in the so-called Diffuser.
[0017] WO 2016/022848 discloses neutron source comprising a
spherical metallic target and a spherical reflector-moderator
surrounding the target, the target and the reflector-moderator
being immersed in a medium containing the material to activate.
[0018] With the neutron source of WO 2016/022848, the material is
randomly activated which increases the time for activating the
material and prevents large amounts of activated material to be
obtained. In addition, recovery of the activated material is
complex and not adapted to radioisotopes suitable for nuclear
medicine therapy with short half-lives as the case for the present
invention. The neutron activator configuration, especially the
reflector position of WO 2016/022848 will not allow favorable
activation yield for radioisotopes other than Mo-99, as produced by
the following neutron capture reaction Mo-98(n,.gamma.)Mo-99. The
size of the reflector and potential based material (like
heavy-water presented in the description) implies industrial and
maintenance complexity as well as preventing from a compact
process. Finally the cooling process involved cryogenic method that
as opposite to the use of water cooling will led to much more
complex usage and maintenance.
[0019] Another object of the disclosure is therefore to provide an
improved system compared to the activator disclosed in WO 98/59347,
WO 2016/037656 and WO 2016/022848.
SUMMARY
[0020] These and other objects are achieved by the presently
disclosed neutron activator for neutron activation of a material,
the neutron activator being configured to produce neutrons from an
interaction with a proton beam emitted along a beam axis, the
proton beam having an energy comprised between 16 MeV and 100 MeV,
preferably 30 MeV and 70 MeV and a beam intensity up to 1 mA,
preferably up to 350 .mu.A for 70 MeV and up to 1 mA for 30 MeV,
the neutron activator comprising: [0021] a neutron source
comprising a metallic target presenting a longitudinal axis
intended to be arranged parallel, and especially coaxial, to the
beam axis, and [0022] a Beryllium reflector-moderator peripheral to
the neutron source and comprising a neutron activation area
configured to accommodate the neutron source and the material to be
activated, the neutron activation area of the Beryllium
reflector-moderator comprising a bore extending along a bore axis
and configured to accommodate the neutron source so that the bore
axis and the longitudinal axis are coaxial.
[0023] The neutron activation area of the Beryllium
reflector-moderator may further include at least one activation
channel extending along a channel axis parallel to the bore axis at
the vicinity of the bore, the activation channel being configured
to load the material to be activated.
[0024] The neutron activation area may comprise a plurality of
activation channels distributed, especially equally distributed,
around the bore.
[0025] The metallic target may have a hollow conical shape, the
longitudinal axis of said conical target being aligned with the
proton beam and the neutron activator further comprises a cooling
area in direct contact with the outer surface of the target for
receiving a flow of fluid for cooling the target during neutron
generation. Said cooling fluid may be a liquid, for example water.
Provisions as to the shape of the metallic target could be
complementary or alternative to the aforementioned provisions
regarding the Beryllium reflector-moderator. That is, the shape of
the metallic target could be provided independently of the
provisions regarding the Beryllium reflector-moderator.
[0026] In such embodiment, the aperture of the conical target and
the thickness of its lateral walls may be optimized so that
[0027] (i) part of the protons received from the proton beam have
sufficient energy to release the fraction of the thermal energy
corresponding to the Bragg peak outside the target,
[0028] (ii) the power density inside the target is reduced to at
least 50% as compared to the power density in a target where all
the protons received from the proton beam release their thermal
energy inside the target, and
[0029] (iii) the number of generated neutrons in the target is at
least 70% equal to the number of generated neutrons in a target
having a thickness where all the protons received from the proton
beam release their thermal energy inside the target.
[0030] Alternatively, the aperture of the conical target and the
thickness of its lateral walls may be optimized so that
[0031] (i) the protons received from the proton beam lose all their
energy within the metallic target, and
[0032] (ii) the stresses generated by the temperature gradients in
the target remain within the elastic limit of the metallic target,
while still keeping the cooling liquid temperature below the
boiling point.
[0033] Advantageously, the aperture of the hollow conical target is
comprised between 20.degree. and 45.degree..
[0034] The neutron activator may further comprise, housed in the
reflector-moderator: [0035] an inlet channel conveying the cooling
fluid to a flow guide, [0036] a flow guide delimiting the cooling
area for guiding the cooling fluid along the outer surface of the
target and obtain the desired velocity as a flow from the inlet
channel to the outlet channel, [0037] an outlet channel for
removing the cooling fluid from the flow guide.
[0038] Preferably, the above-defined flow guide is at least partly
conical so that said conical flow guide covers the outer surface of
the conical target thereby delimiting a cooling area surrounding
the outer surface of the target.
[0039] In specific embodiments which can be combined with any of
the previous embodiments, the metallic target is made of Beryllium
or Tantalum.
[0040] In a specific embodiment which can be combined with any of
the previous embodiments, the Beryllium reflector-moderator is
cylindrical along the bore axis.
[0041] Typically, the neutron activator may present an overall
dimension that does not exceed the volume of a cube of 1 meter
side, preferably 0.75 meter side, and for example 0.50 meter
side.
[0042] The neutron activator may further comprise a second
reflector-moderator embedding said Beryllium
reflector-moderator.
[0043] The invention also relates to a neutron activation system
for neutron activation of a material, comprising: [0044] a
generator configured to produce a proton beam along a beam axis,
the proton beam having an energy comprised between 16 MeV and 100
MeV, preferably 30 MeV and 70 MeV and a beam intensity up to 1 mA,
preferably up to 350 nA for 70 MeV and up to 1 mA for 30 MeV,
[0045] a neutron activator as defined previously arranged so that
the longitudinal axis of the target is parallel, especially
coaxial, to the beam axis.
[0046] When the neutron activation area of the Beryllium
reflector-moderator includes at least one activation channel, the
neutron activation system may further comprises a supplying device
for loading the material to be activated, the supplying device
being connected to the activation channel and configured to move
samples of material to be activated along the activation
channel.
[0047] The present invention also relates to the use of the neutron
activator as previously described, for producing radioisotopes,
preferably radiopharmaceuticals. For example, said radioisotope is
a .beta..sup.- emitting radioisotope suitable for Nuclear Medicine
applications, preferably .sup.166Ho, .sup.186Re, .sup.188Re,
.sup.177Lu, .sup.198Au, .sup.90Y, .sup.227Ra and .sup.161Tb.
[0048] Another object of the present invention is a method for
neutron activation of a material, said method comprising:
[0049] a) providing the material to be activated,
[0050] b) placing the material at the activation area of a neutron
activator as defined previously,
[0051] c) generating a proton beam at an energy suitable for
neutron activation of said material, thereby activating said
material.
[0052] In a specific embodiment of the above-defined method using a
neutron activator with a conical target as described above, the
target is cooled by a flow of cooling liquid, preferably water, at
a static pressure comprised between 1 and 20 Bar and reaching, near
the target surface, speeds comprised between 8 and 15 m/s.
[0053] In another specific embodiment of the method, said material
to be activated is contained within or in the form of a
microparticle or nanoparticle, for example of Holmium-oxide
micro/nanoparticles. Typically, the micro/nanoparticles are in a
liquid suspension.
[0054] In a specific embodiment, said material is contained in a
capsule, and said capsule is placed at the activation area by
moving the capsule within an activation channel embedded in the
reflector-moderator.
BRIEF DESCRIPTION OF THE DRAWINGS
[0055] The invention will be understood more clearly with the
following detailed description of a preferred but non-limiting
embodiment. This detailed description is given with reference to
the attached drawings, in which:
[0056] FIG. 1 is a schematic illustration of the neutron activator
according to the present disclosure,
[0057] FIG. 2 is a schematic illustration of a cylinder-shaped
target assembly including the hollow conical target and its cooling
system,
[0058] FIG. 3 is a schematic illustration of the method for neutron
activation using a neutron activator according to the present
disclosure,
[0059] FIG. 4 is an illustration of the activation samples
positions with respect to the hollow conical target
[0060] FIG. 5 is a graph presenting the cross-sections for the
.sup.165Ho(n,.gamma.).sup.166Ho and the .sup.176
Lu(n,.gamma.).sup.177Lu transmutations,
[0061] FIG. 6 is a graph presenting the neutron spectra with
various moderators.
DETAILED DESCRIPTION
[0062] The present disclosure relates to a neutron activator for
neutron activation of a material comprising: [0063] a neutron
source comprising a metallic target suitable for receiving a proton
beam of energy comprised between 16 and 100 MeV, preferably between
30 and 70 MeV, and capable of sustaining beam intensities up to
1:mA, preferably up to 350 .mu.A for 70 MeV and up to 1 mA for 30
MeV and [0064] a Beryllium first reflector-moderator peripheral to
the neutron source and comprising a neutron activation area, [0065]
optionally, a second reflector-moderator embedding said Beryllium
reflector-moderator.
[0066] The neutron activator according to the invention
advantageously provides an optimized flux of neutrons having the
energy of interest in the localized area around the samples to be
activated, while remaining sufficiently compact for its use with
small-medium sized cyclotrons.
[0067] It is therefore appropriate to perform a routine and
industrial production of activated doses of radioisotopes, for use
in pre-clinical and clinical studies, as well as for product
commercialization.
[0068] An embodiment of the neutron activator according to the
present disclosure is illustrated at FIG. 1.
[0069] More specifically, a neutron activator of the present
disclosure may comprise: [0070] a metallic hollow conical target as
neutron source, [0071] a cooling system including a flow guide and
a cooling container for guiding a cooling fluid along the outer
surface of the conical target, [0072] a first Beryllium
reflector-moderator surrounding the cooling container and hosting
the activation channels disposed around the target, [0073] a second
reflector-moderator embedding the first Beryllium
reflector-moderator.
[0074] In particular, the neutron activator may comprise, housed in
the reflector-moderator: [0075] a metallic hollow conical target as
neutron source, [0076] a flow guide delimiting the cooling area,
for guiding the cooling fluid along the outer surface of the
target, as a flow from an inlet channel to an outlet channel,
[0077] an inlet channel conveying the cooling fluid to the flow
guide, [0078] an outlet channel for removing the cooling fluid from
the flow guide.
[0079] An example of a cylinder-shaped target assembly including
the hollow conical metallic target and its cooling system is
provided in FIG. 2. In such specific embodiment, the target as
neutron source is a hollow conical metallic target which
longitudinal axis is aligned with the beam axis of the proton beam.
The cooling system includes (i) a cooling container delimiting an
inlet channel and an outlet channel for circulation of the cooling
fluid, and (ii) a flow-guide delimiting the cooling area for
guiding the cooling fluid along the outer surface of the hollow
conical metallic target, as a flow from the inlet channel to the
outlet channel.
[0080] The Metallic Target as Neutron Source
[0081] The neutron source is made of a metallic target presenting a
longitudinal axis intended to be arranged parallel to the beam axis
of the proton beam for receiving the proton beam which is
advantageously generated by a cyclotron. In the represented
embodiment, the longitudinal axis and the beam axis are coaxial,
namely superposed. In other embodiments, the longitudinal axis and
the beam axis could be parallel and spaced apart from each
other.
[0082] Accordingly, the target body should be capable of sustaining
proton beam of low energy and high intensity, for example, a proton
beam energy comprised between 16 and 100 MeV, preferably between 30
and 70 MeV and beam intensities up to 1 mA, preferably up to 350
.mu.A for 70 MeV and up to 1 mA for 30 MeV.
[0083] Embodiment with Conical Target Body
[0084] The target body preferably has a hollow conical shape. The
conical shape of the target when aligned with the proton beam
enables to optimize the yield of neutrons reaching the activation
area surrounding the target. In particular, a conical shape of the
target with a small aperture angle advantageously increases the
interaction surface between the proton beam and the inner surface
of the target, thereby lowering the power density in the target
while increasing the surface for thermal cooling.
[0085] As used herein, the term "conical shape" is used with his
broad meaning and refer to cones of circular or non-circular bases
(for example the base could be of polygonal or elliptic or any
other shape). In a preferred embodiment, the conical shape is a
right circular cone.
[0086] As used herein, the term "hollow" conical shape means that
the target is open at its base and essentially consists of the
lateral walls of the cone.
[0087] The longitudinal axis of said hollow conical target is
aligned with the proton beam generated by a cyclotron. Accordingly,
the proton beam reaches the hollow conical target from the inner
surface of the lateral walls of the conical target.
[0088] The neutron activator advantageously further comprises a
cooling area in direct contact with the outer surface of the
conical target for receiving a flow of fluid for cooling the target
during neutron generation.
[0089] The final dimensions of the hollow conical metallic target
and the cooling area will be adapted with the aim of optimizing the
generation of neutrons.
[0090] In an embodiment of the neutron activator, the aperture of
the conical target and the thickness of its lateral walls are
preferably optimized so that part of the protons received from the
proton beam have sufficient energy to release the fraction of the
thermal energy corresponding to the Bragg peak outside the target
in the cooling area, where this heat is easily removed by the
cooling flow. This allows to significantly reduce the power density
in the solid target, and so improve the target thermal conditions,
without significantly reducing the neutron generation
[0091] Preferably, at least 50% of the energy coming from the
interacting protons is lost outside the target as compared to the
energy deposited inside the target if this one would have a
thickness where all the protons received from the proton beam
release their thermal energy inside it.
[0092] In such embodiment, the aperture and thickness of the
conical target are optimized so that the power density is
preferably reduced to at least 50% as compared to the power density
in a conical target with aperture and thickness where all the
protons would release their thermal energy inside the target.
[0093] Additionally, the aperture and thickness of the conical
target will be determined so that the number of generated neutrons
in the target is at least 70% equal to the number of generated
neutrons in a target where all the protons received from a proton
beam would release their thermal energy inside the target.
[0094] Depending on (i) the shape of the conical target, (ii) the
nature of the metal used for the target and (iii) the energy and
intensity of the proton beam, the skilled person will be able to
determine the above optimized ranges for thickness and aperture of
the target, using any appropriate simulation software, and thereby
reaching optimized yield for neutron activation using a compact
neutron activator.
[0095] In a specific embodiment where the target has a right
circular conical shape and is of Beryllium metal and the energy of
the proton beam is between 65 and 75, for example 70 MeV, with an
intensity between 0.30 and 0.40 mA, typically 0.35 mA, the
thickness of the lateral walls is preferably between 4 and 4.6 mm,
for example 3.6 mm, the axial thickness 22.5 and 27.5 mm, typically
25 mm and the aperture of the conical target is preferably between
18 and 22.degree., for example 20.degree.. The circular base of the
target may be set between 27 and 33, for example 30 mm, in order to
be adapted to typical beam-line size of 70 MeV cyclotrons.
[0096] Alternatively, in a second embodiment of the neutron
activator, the aperture of the conical target and the thickness of
its lateral walls are optimized so that [0097] (i) the protons
received from the proton beam lose all their energy within the
metallic target, and [0098] (ii) the stresses generated by the
temperature gradients in the target remain within the elastic limit
of the metallic target.
[0099] This embodiment may be appropriate when the proton beam
characteristics (in terms of energy, intensity and width/current
distribution) do not result in very high power densities in the
solid target, as for example in the case of a 30 MeV-185 .mu.A-30
mm beam on a water-cooled conical Beryllium or 30 MeV-140 .mu.A-30
mm beam on a water-cooled conical Tantalum target.
[0100] In the latter embodiment, if a liquid such as water is used
as a cooling fluid, it is indeed necessary to limit the thermal
stress for avoiding the boiling of the cooling liquid and/or the
deformation of the target.
[0101] The metallic target should be made of a material which
thickness and composition allow an efficient neutron production,
combined with good thermo-mechanical properties. Appropriate
material includes without limitation Beryllium, Tantalum, Tungsten
and its alloys (e.g. Tungsten-Rhenium or Tungsten-Copper).
[0102] Typically, the metallic target may be made of Beryllium.
[0103] In another specific embodiment, the metallic target is made
of Tantalum. In such embodiment, the redox phenomenon typical of
Tantalum at temperatures higher that 100.degree. C. can be avoided
by exposure of the inner surface of the lateral walls of the
conical target to a vacuum atmosphere at a pressure of 10.sup.-3
mbar or lower (small oxygen concentration), while the temperature
of the outer surface in contact with water as cooling fluid is kept
below 200.degree. C. by the cooling effect of the water itself.
[0104] A preferred embodiment of the hollow conical target and its
cooling system is illustrated in FIG. 2.
[0105] In such preferred embodiment, the cooling system comprises
[0106] a flow guide and [0107] a cooling container.
[0108] In this preferred embodiment, the flow guide is in close
proximity to the outer surface of the conical target and thereby
delimits a cooling area for guiding the cooling fluid all along the
outer surface of the conical target. The flow guide is connected to
the cooling container which includes: [0109] an inlet channel for
conveying the cooling fluid to the flow guide and [0110] an outlet
channel for removing the cooling fluid from the flow guide.
[0111] More specifically, the flow guide is at least partly
conical, preferably with similar shape to the conical shape of the
target, so that said conical flow guide covers the outer surface of
the conical target thereby delimiting a cooling area surrounding
the outer surface of the target, sized in order to obtain along the
target walls an optimized velocity distribution of the cooling
liquid.
[0112] In a particular embodiment, there is no direct contact
between the target and the flow guide so that the cooling fluid can
contact all the outer surface of the target.
[0113] Advantageously, the assembly of the hollow conical target
with the flow guide and the cooling container is cylinder-shaped so
that it can be readily housed in the reflector-moderator
surrounding said target assembly.
[0114] In a specific embodiment, thermocouples may be placed on or
inserted al the outer surface of the target, for example at the
base of the cone, for monitoring the thermal status of the
target.
[0115] The Beryllium Reflector-Moderator
[0116] The neutron activator according to the present disclosure
further includes a reflector-moderator which is peripheral to the
neutron source and therefore, surrounds the target and its cooling
system. The reflector-moderator further comprises the neutron
activation area. Its function is to concentrate the activated
neutrons in the area containing the activation samples (activation
area) while efficiently slowing-down (moderating) the neutrons down
to energies suitable for the activation of the selected
isotopes.
[0117] The reflector-moderator is made of Beryllium or contains at
least 90% of Beryllium metal. As shown in the example, the use of
Beryllium as material for the reflector-moderator presents
different advantages compared with other materials: [0118] it
presents a good capacity for containing the neutrons in some
defined spectra, and thereby an improved activation efficiency in
the activation area, [0119] it is more adapted for activating the
radioisotopes of interest, mainly Holmium particles.
[0120] The first reflector-moderator is hence configured to
accommodate the neutron source and the material to be activated.
The neutron activation area of the first reflector-moderator
comprises a bore extending along a bore axis and configured to
accommodate the neutron source so that the bore axis and the
longitudinal axis are coaxial.
[0121] For example, in one specific embodiment of the neutron
activator, the reflector-moderator surrounds a cylinder-shaped
assembly of a hollow conical target and its cooling system (target
assembly), said target assembly including [0122] a right circular
conical target, [0123] a flow guide with similar conical shape to
the target, and, [0124] a cylinder-shaped cooling container as
described in the previous sections.
[0125] In such specific embodiment, the reflector-moderator is
cylindrical of circular cross-section, along the bore axis.
Alternatively, the reflector-moderator may be cylindrical along the
bore axis of any suitable other cross-section.
[0126] The dimensions of the reflector-moderator are set as to
maximize the activation yield of the isotopes while keeping it as
small as possible. Advantageously, the activator including the
neutron source, the reflector-moderator, optionally together with
the second reflector-moderator, has an overall dimension that does
not exceed the volume of a cube of 1 meter side, preferably 0.75
meter side, and for example 0.50 meter side.
[0127] The reflector-moderator further includes activation channels
for loading the material to be activated at the neutron activation
area. The activation channels should enable the loading and
unloading of the material to be activated. Said channels may be
machined within the reflector-moderator. The skilled person will
know how to determine the positions of said activation channels
with respect to the target using appropriate simulations, in order
to optimize the activation of the radioisotopes.
[0128] In a specific embodiment where the hollow conical target and
its cooling system is cylinder-shaped (as described above), a
plurality of activation channels may be disposed on concentric
rings around the target.
[0129] More particularly, the activation area of the first
reflector-moderator also comprises several activation channels
extending along a channel axis parallel to the bore axis at the
vicinity of the bore. In particular, the activation area comprises
activation channels distributed around the bore. The activation
channels are equally distributed around the bore. For example, in
the represented embodiment, a first series of activation channels
are evenly distributed around the bore at a first distance from the
bore axis and a second series of activation channels are evenly
distributed around the bore at a second distance from the bore
axis, greater than the first distance.
[0130] Advantageously, the neutron activator further includes a
remote material loading system, for allowing the remote
loading-unloading of the material to be activated within the
activation channels.
[0131] Although disclosed in relation with a target having a
conical shape, the provisions as to the Beryllium
reflector-moderator could be provided independently of the
provisions regarding the shape of the target.
[0132] The Second Reflector-Moderator
[0133] The second reflector-moderator embedding the Beryllium
reflector-moderator aims at further slowing down and scattering
back the neutrons, already partially moderated, escaping the
Beryllium reflector-moderator. Its main purpose is to optimize the
activator performances while minimizing the volume, and therefore
the cost, of the very expensive Beryllium reflector-moderator.
[0134] Preferably, the second reflector-moderator may be made of
polyethylene, typically high-density polyethylene. The dimensions
of the moderator will be such that the assembled activator,
including the target, its cooling system, the reflector-moderator
and the second reflector-moderator does not exceed a volume of a
cube of 1 meter side, preferably 0.75 meter side, and for example
0.50 meter side.
[0135] Method for Neutron Activation
[0136] The activator according to the invention is dedicated to
neutron activation of particles.
[0137] Therefore, another object of the present invention is to
provide a method for neutron activation of a material, said method
comprising:
[0138] a) providing the material to be activated,
[0139] b) placing the material at the activation area of a neutron
activator as described in the present disclosure,
[0140] c) generating a proton beam at an energy suitable for
neutron activation of said material, thereby activating said
material.
[0141] In a specific embodiment, said material to be activated is
contained within or in the form of a micro or nanoparticles, for
example of Holmium-oxide micro or nanoparticles. Examples of
Holmium-oxide particles are described in "New modality of
curietherapy with holmium oxide submicronic particles." EANM 2009,
Annual Congress of the European Association of Nuclear Medicine,
Oct. 10-14, 2009, Barcelona, Spain
[0142] Preferably, the microparticles or nanoparticles are in a
liquid suspension.
[0143] For example, said material may be contained in a capsule,
and said capsule is placed at the activation area by moving the
capsule within the activation channels embedded in the
reflector-moderator.
[0144] FIG. 3 represents an embodiment of a neutron activation
system comprising: [0145] a generator, such as a cyclotron 13,
configured to produce a proton beam along a beam axis, the proton
beam having an energy comprised between 16 MeV and 100 MeV,
preferably 30 MeV and 70 MeV and a beam intensity up to 1 mA,
preferably up to 350 .mu.A for 70 MeV and up to 1 mA for 30 MeV,
[0146] a neutron activator arranged so that the longitudinal axis
of the target is parallel, especially coaxial, to the beam axis, to
produce neutrons from the interaction with the proton beam and to
activate the material to be activated, and [0147] a supplying
device for loading one or more samples of material to be
activated.
[0148] The method according to the invention is disclosed in
relation with the neutron activation system of FIG. 3 which
represents the different steps of the neutron activation.
[0149] Samples of material to be activated (activation samples)
such as microparticles containing stable targeted isotopes are
provided in the form of suitable capsules (15). The capsules are
then loaded in the activation channels (5) through the supplying
device which may include for example a shielded capsule loader (16)
and a transfer system (14).
[0150] The supplying device is connected to the activation channels
(5) and configured to move, preferably in an automated manner,
samples of material to be activated along the activation channel
(5). Advantageously, the method comprises the use of a pneumatic
loading and unloading system, allowing the remote loading-unloading
of the capsule(s) within the activation channels. For example, the
capsules travel back and forth through a compressed air rabbit
system allowing the remote loading/unloading of the particles
suspension capsules. More advantageously, the pneumatic system
allows also the cooling, by means of a flux of air flowing in all
activation channels, of the heat generated by the interactions of
the neutrons with the capsules and their content during the
irradiation.
[0151] A proton beam (7) for example with energy between 16 and 100
MeV, preferably 30 and 70 MeV and intensities up to 1 mA,
preferably up to 350 .mu.A for 70 MeV and up to 1 mA for 30 MeV is
then generated by a cyclotron (13).
[0152] The proton beam is directed to the metallic target (1) and
the protons interact with the metallic target (for example made of
Be), thereby generating fast (high energy) neutrons (12).
[0153] The target is cooled in the cooling area, using for example
water flowing from an inlet channel to the outer surface of the
target (2). In a specific embodiment, the target is cooled by a
flow of cooling liquid, preferably water, at a static pressure
comprised between 1 and 20 bar and reaching, near the target
surface, speeds comprised between 8 and 24 mis. The cooling aims at
avoiding the boiling of the water while limiting erosion effects on
the surface of the solid target or relevant vibration of the target
structure. The cooling-water volume has the additional effect of
giving a first moderation to the high-energy neutrons flowing out
from the target. The relevance of this moderating effect depends on
the thickness of the water layer. However in a specific embodiment
of the activator design, the water-layer thickness is minimised at
the advantage of keeping the activation samples as close as
possible to the target and the beryllium reflector as compact as
possible.
[0154] The neutrons are reflected and moderated in the first
reflector-moderator (4) for reaching the activation area (10).
Neutrons passing through the first reflector-moderator may be
further moderated and scattered back by the second
reflector-moderator (6).
[0155] The method for neutron activation according to the invention
presents at least the following advantageous aspects: [0156] it is
possible to activate the particles in injectable form, which is
hardly achievable with a nuclear reactor, [0157] the use of a
dedicated cyclotron-driven system allows a more flexible production
and distribution of activated radioisotopes, [0158] no particles
damage due to .gamma.-heating (typical of nuclear reactors) occurs,
[0159] short-life isotopes can be used and repeated treatment can
be planned to increase the therapeutic efficiency, [0160] different
types and sizes of nanoparticles can be used to tailor the therapy
method to the specific case.
[0161] Use of the Neutron Activator
[0162] The present invention also relates to the use of the neutron
activator as previously described, for producing radioisotopes,
preferably for use in radiopharmaceuticals and medical devices.
[0163] The choice of the radioisotopes depends on three main
characteristics: the half-life, the .beta..sup.31 energy and the
.gamma. energy (Table 1). Shorter half-life allows shorter
permanence period in the treating unit (repeated treatment
possible). Higher .beta..sup.- energy corresponds to higher
therapeutic efficiency. Higher.sub.7 energy corresponds to better
detection with Single photon emission computed tomography
(SPECT).
TABLE-US-00001 TABLE 1 Radioisotope Half-life .beta..sup.-
energy(keV) .gamma. energy (keV) Holmium 166 26.7 hours 1840 80
Lutetium 177 6.7 days 497 208 Rhenium 186 3.7 days 1077 137 Rhenium
188 17 hours 2100 155 Yttrium 90 2.7 days 2080 No Gold 198 2.7 days
1372.9 411.8 Terbium 161 6.9 days 157.4 74.5
[0164] In a specific embodiment, said radioisotope is a
.beta..sup.- emitting radioisotope suitable for Nuclear Medicine
applications, preferably .sup.166Ho, .sup.186Re, .sup.188Re,
.sup.177Lu, .sup.198Au, .sup.90Y, .sup.227Ra and .sup.161Tb.
[0165] Holmium is of particular interest for the application of the
present invention as it represents a very good compromise combining
a short half-life and high .beta..sup.- energy, compared with the
other radioisotopes.
DESCRIPTION OF A SPECIFIC EMBODIMENT OF THE METHOD AND THE DEVICE
ACCORDING TO THE INVENTION
[0166] The activator according to the Example, represented in FIG.
1, is a rectangular parallelepiped with a 50 cm width, 50 cm
height, and 56 cm long. It is composed of: [0167] a hollow
Beryllium conical target (1), [0168] a flow guide (2), an inlet
channel (8) for conveying the cooling fluid to the flow guide (2)
and an outlet channel (9) for removing the cooling fluid from the
flow guide (2), [0169] a cylinder shaped cooling container (3) with
an inlet and outlet channel, [0170] a Beryllium cylindrical
reflector-moderator (4) with an internal diameter Di=100 mm, an
external diameter De=-160 mm and a length of 200 ram, hosting the
activation channels (5) disposed coaxially around the target (1),
[0171] a high density polyethylene second reflector-moderator
(6).
[0172] The activation channels (5) are disposed on rings placed in
a concentric way around the target. One ring of 16 channels allows
a total loading capacity of 64 capsules/doses (4 per channel).
[0173] Table 2 presents the technical parameters of the
activator.
TABLE-US-00002 TABLE 2 PARAMETER VALUE RATIONALE Beam Beam type
Protons Best neutron yield Beam Energy 70 MeV Maximize neutron
yield Beam current 350 .mu.A Maximize neutron yield Beam current
Gaussian with Ref assumption for most ref distrib. FWHM = 1.4431
challenging cooling conditions, real shape to be determined
Collimators 30 mm Minimize power density diameter Target Material
Be Maximize neutron yield, assure resistance minimize activation
Shape Hollow cone Optimize heat exchange Overall D = 35 mm Optimize
heat exchange dimensions H = 119.6 mm Moderator- Material Be/PEHD/
Optimize neutron fluxes reflector Water and spectrum Shape
cylindrical Be moderator- height = 20 cm reflector diameter =
dimensions 16 cm PEHD cube 0.5 .times. 0.5 .times. 0.6 m dimensions
Activation Dimensions D = 11 mm Minimize neutron leak channels
Number 16 Maximize loading capacity Capsules per 1 / 4 Maximize
loading capacity channel Activation Material Peek/LDPE capsules
Dimensions Diameter 8.5 mm Length 45 mm
[0174] To limit erosion effects, the cooling water velocity has
been limited at around 10 m/s, corresponding, with the present
dimensions, to a flow rate of about 2 kg/s. With this condition,
the maximum temperature of the wall at the interface target/water
is expected around 150.degree. C. To avoid boiling, the coolant
(water) has to be pressurized at least at 5 bars.
[0175] Table 3 summarizes the cooling characteristics for the Be
target.
TABLE-US-00003 TABLE 3 Properties Value Target maximum temperature
250.degree. C. Maximum temperature at the interface target/water
150.degree. C. Maximum boundary heat flux 8 MW/m.sup.2 Minimum
pressure needed in the cooling system 5 bar Mass flow rate 2
kg/s
[0176] In order to choose the best material for the
reflector-moderator placed around the target and hosting the
activation channels, a set of Monte Carlo calculations was done by
comparing the following materials: water, polyethylene, beryllium,
graphite and lead.
[0177] Given the cross-section for the
.sup.165Ho(n,.gamma.).sup.166Ho transmutation (reported in FIG. 4
together with the one for the .sup.176Lu(n,.gamma.).sup.177Lu),
most favorable neutron energies are in the thermal (0-10.sup.-7
MeV) and epithermal (10.sup.-7/ 5.times.10.sup.-3 MeV) range.
[0178] As shown in the graph of FIG. 5 representing the neutron
spectra in activation channel as shown in FIG. 4, the resulting
neutron spectrum is most favorable in the case of the Beryllium,
which shows [0179] as can be seen by comparing the total neutron
fluxes for Be and Pb, the higher neutron absorption of the Be is
compensated by a better neutron-confinement, resulting in a total
neutron flux comparable to Pb, [0180] furthermore, Be shows very
good moderation, yielding significantly higher fluxes in the
thermal region with respect to all the other materials, and same
level as Pb in the epithermal region.
[0181] As a result presented in table 4, the .sup.166Ho activation
yield is significantly better with the Be reflector-moderator.
TABLE-US-00004 TABLE 4 Reflector-moderator Saturation Activity
(Bq/g/uA) Water 3.88E+08 Polyethylene 4.27E+08 Beryllium 9.19E+08
Graphite 4.33E+08 Lead 6.56E+08
[0182] With this activator according to the Example replacing the
hollow Beryllium conical target by a hollow Tantalum conical
target, the .sup.166Ho activation yield is much higher with the Be
reflector-moderator as presented in table 5.
TABLE-US-00005 TABLE 5 Reflector-moderator Saturation Activity
(Bq/g/uA) Beryllium 2.1E+09
* * * * *