U.S. patent application number 17/825217 was filed with the patent office on 2022-09-22 for system, emanation generator, and process for production of high-purity therapeutic radioisotopes.
This patent application is currently assigned to BATTELLE MEMORIAL INSTITUTE. The applicant listed for this patent is BATTELLE MEMORIAL INSTITUTE. Invention is credited to Matthew J. O'Hara.
Application Number | 20220301737 17/825217 |
Document ID | / |
Family ID | 1000006377774 |
Filed Date | 2022-09-22 |
United States Patent
Application |
20220301737 |
Kind Code |
A1 |
O'Hara; Matthew J. |
September 22, 2022 |
System, Emanation Generator, and Process for Production of
High-Purity Therapeutic Radioisotopes
Abstract
An isotope production system, emanation generator, and process
are disclosed for production of high-purity radioisotopes. In one
implementation example, high-purity Pb-212 and/or Bi-212 isotopes
are produced suitable for therapeutic applications. In one
embodiment the process includes transporting gaseous radon-220 from
a radium-224 bearing generator which provides gas-phase separation
of the Rn-220 from the Ra-224 in the generator. Subsequent decay of
the captured Rn-220 accumulates high-purity Pb-212 and/or Bi-212
isotopes suitable for direct therapeutic applications. Other
high-purity product isotopes may also be prepared.
Inventors: |
O'Hara; Matthew J.;
(Richland, WA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
BATTELLE MEMORIAL INSTITUTE |
Richland |
WA |
US |
|
|
Assignee: |
BATTELLE MEMORIAL INSTITUTE
Richland
WA
|
Family ID: |
1000006377774 |
Appl. No.: |
17/825217 |
Filed: |
May 26, 2022 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15675529 |
Aug 11, 2017 |
11348702 |
|
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17825217 |
|
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62373661 |
Aug 11, 2016 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
B01J 20/06 20130101;
G21G 2001/0084 20130101; G21G 2001/0094 20130101; C01G 21/00
20130101; G21G 4/08 20130101; C01B 23/0073 20130101; G21G 4/10
20130101; A61K 51/00 20130101; A61K 51/1289 20130101; G21G 1/0005
20130101 |
International
Class: |
G21G 4/08 20060101
G21G004/08; B01J 20/06 20060101 B01J020/06; C01B 23/00 20060101
C01B023/00; C01G 21/00 20060101 C01G021/00; A61K 51/00 20060101
A61K051/00; G21G 4/10 20060101 G21G004/10; G21G 1/00 20060101
G21G001/00; A61K 51/12 20060101 A61K051/12 |
Goverment Interests
STATEMENT REGARDING RIGHTS TO INVENTION MADE UNDER
FEDERALLY-SPONSORED RESEARCH AND DEVELOPMENT
[0002] This invention was made with Government support under
Contract DE-AC05-76RL01830 awarded by the U.S. Department of
Energy. The Government has certain rights in the invention.
Claims
1. An emanation system for production of ultrapure radioisotopes,
comprising: an emanation device having an emanation source
comprising a source isotope therein that emanates a radioactive gas
therefrom; and a collection device configured to collect the
radioactive gas retaining same for a time sufficient to yield one
or more high purity radioactive daughter isotopes therein.
2. The system of claim 1 wherein the source isotope is selected
from Thorium-228 and/or Radium 224; Thorium-227 and/or Radium-223;
or Thorium-230 and/or Radium-226.
3. The system of claim 1 wherein the radioactive gas is selected
from Radon-220; Radon-219; and Radon-222.
4. The system of claim 1 wherein the radioactive gas is a
radioactive noble gas.
5. The system of claim 1 wherein the source isotope is disposed on
a particle surface or a permeable support.
6. The system of claim 1 wherein the source isotope is disposed on
magnetic or paramagnetic metal oxide particles.
7. The system of claim 1 wherein the source isotope is disposed on
a gas-permeable support.
8. The system of claim 1 wherein the collection device includes a
cooling device configured to cool the radioactive gas emanated from
the emanation device.
9. The system of claim 1 wherein the collection device includes a
soluble salt configured as a thin film or a packed salt, or a
lipophilic liquid configured as a thin film or a thin film coating
on a solid support to extract the radioactive gas emanated from the
emanation device therein.
10. The system of claim 1 further including an eluent delivery
device or system configured to deliver a fluid to recover the
radioactive daughter isotopes from the collection device.
11. The system of claim 1 wherein the radioactive daughter isotopes
are selected from Pb 212 and/or Bi-212; Pb-211 and/or Bi-211; and
Pb-214 and/or Bi-214; and daughter isotopes thereof.
12. An emanation system for production of ultra-pure isotopes for
radiotherapeutic applications, comprising: an emanation generator
comprising a radium source configured to generate a radioactive gas
that is emitted separating same therefrom; and a collection device
configured to collect and retain the emitted radioactive gas for a
time sufficient to decay the gas therein yielding one or more
radioactive daughter isotopes therefrom.
13. A method of producing high purity radioisotopes, comprising the
steps of: emanating a radioactive gas generated in a source
material comprising a source isotope to separate the radioactive
gas as a pure product therefrom; and collecting the separated
radioactive gas and retaining same for a time sufficient to decay
the radioactive gas to yield one or more high purity radioactive
daughter isotopes therefrom.
14. The method of claim 13 wherein the source isotope is selected
from Thorium-228 and/or Radium 224; Thorium-227 and/or Radium-223;
or Thorium-230 and/or Radium-226
15. The method of claim 13 wherein the radioactive gas is selected
from Radon-220; Radon-219; and Radon-222.
16. The method of claim 13 wherein the radioactive gas is a
radioactive noble gas.
17. The method of claim 13 wherein the collecting step includes
cooling the emanated radioactive gas with a cooling device or
cryogen to condense or deposit the emanated radioactive gas.
18. The method of claim 13 wherein the collecting step includes
extracting the radioactive gas on a thin film or a packed column
comprising a soluble salt; or in a thin film or thin film coating
comprising a lipophilic material on a solid support.
19. The method of claim 13 wherein the radioactive daughter
isotopes are selected from Lead 212 and/or Bismuth-212; Lead 211
and/or Bismuth-211; and Lead-214 and/or Bismuth-214 and daughter
isotopes thereof.
20. The method of claim 13 further including the step of recovering
the radioactive daughter isotopes in a fluid such as a
biologically-compatible aqueous solution.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This is a non-provisional application that claims priority
from U.S. Provisional Patent Application No. 62/373,661 filed 11
Aug. 2016 entitled "Gas Emanation System, Generator, and Process
for Production of High-Purity Radioisotopes" which is incorporated
in its entirety by reference herein.
FIELD OF THE INVENTION
[0003] This disclosure relates to production of high purity
radionuclides.
BACKGROUND OF THE INVENTION
[0004] The alpha emitting radionuclide bismuth-212 (Bi-212)
[half-life=60.6 min.], a daughter product of lead-212 (Pb-212)
[half-life=10.6 hrs.], is a promising radionuclide for use in
targeted alpha therapy. Pb-212 can be used as an in vivo generator
of Bi-212 giving labeled antibodies time to locate and bind to
cancer cells while the Bi-212 isotope is generated thus
facilitating a longer therapy. Bi-212 can also be utilized as a
therapeutic isotope independent of its Pb-212 parent. An added
advantage of the Pb-212 and/or Bi-212 isotopes is the relatively
abundant sources of natural thorium-232 (Th-232) and legacy sources
such as thorium-228 (Th-228) and uranium-232 (U-232) that can
provide alpha isotopes for current and future therapy needs.
Current generators for producing Pb-212 and/or Bi-212 isotopes are
column-based generators that employ source isotopes such as Th-228
and/or radium-224 (Ra-224) (the immediate decay daughter of Th-228)
that are adsorbed onto a cation exchange resin in an exchange
column from which the Pb-212 and/or Bi-212 isotopes are recovered
from the resin. However, while generators that employ a Th-228
source isotope (half-life=1.9 yrs) can provide a long-term supply
of Pb-212 and Bi-212 isotopes, these generators have well-known
problems. First, Th-228 generators are high-activity generators
that can cause radiolytic failure in the generator columns over
time and release high energy contaminates into the Pb-212 and/or
Bi-212 solutions recovered from these columns that can deliver
deleterious radiation doses. Th-228 generators in the prior art
also experience characteristic decreases in radon yields over time
due to radiolytic breakdown of organic capture materials such as
barium-stearate utilized to contain the isotope sources. Severe
contamination can also result if a breach in the generator column
takes place due to prolonged radiolysis by the high energy source
isotopes therein. Generators that employ Ra-224 as a source isotope
are considered a generally safer source of Pb-212 and Bi-212
isotopes compared to Th-228 generators given their considerably
shorter half-life (3.6 days). The U.S. Department of Energy's
National Isotope Development Center (NIDC) supplies Ra-224
generators in which the Ra-224 source isotopes are separated and
purified from a Th-228 and/or U-232 stock solution and again
adsorbed onto a cation exchange resin in an exchange column.
Daughter products Pb-212 and/or Bi-212 generated from the decay of
Ra-224 and Rn-220 are periodically eluted from the column using
acidic solutions such as hydrochloric or hydriodic acid or mixtures
of these acids. However, exchange resins utilized in these
generators are also prone to radiolytic breakdown that can result
in breakthrough of Ra-224 isotopes from the generator column that
contaminate solutions containing the recovered Pb-212 and/or Bi-212
isotopes. This again can result in unnecessary or unacceptable
radiation doses to the patient. Additionally, these generators can
demonstrate low Pb-212 and/or Bi-212 yields due to gaseous
diffusion of the intermediate noble gas daughter Rn-220 deep into
the exchange resin beads in-situ. Accordingly, new generator
sources and processes are needed for production of high-purity
therapeutic radioisotopes and other similar isotopes.
SUMMARY
[0005] This disclosure details an isotope production system,
emanation generator, and process for production of high purity
isotopes including those utilized for therapeutic applications. The
isotope production system, emanation generator, and process address
various problems in prior art isotope production systems including
eliminating radiolytic degradation and breakthrough of high energy
isotopes such as Ra-224 and Th-228 that can contaminate recovered
isotopes; and eliminating reduction in isotope yields in prior art
generators caused by radiolytic breakdown of organic capture
materials and diffusion of radon gas into organic capture
materials. In one embodiment, the emanation system includes an
emanation device or generator having an emanation source loaded
with a source isotope that generates a radioactive gas that is
released and emanated from the emanation source device which
separates the emanated radioactive gas from the source isotope as a
pure radioactive gas product and a collection device or system that
collects the radioactive gas and retains the gas for a time
sufficient to decay and from one or more high purity radioactive
daughter isotopes therein. The source isotope can include thorium
isotopes, radium isotopes, and combinations of thorium and radium
isotopes. Exemplary source isotopes include Thorium-228 (Th-228)
and/or Radium-224 (Ra-224); Thorium-227 (Th-227) and/or Radium-223
(Ra-223); or Thorium-230 (Th-230) and/or Radium-226 (Ra-226) and
combinations thereof. The source isotope can be sorbed or deposited
onto particle surfaces or a permeable support such as a
gas-permeable support and utilized in the emanation source. The
source isotope can also be sorbed or deposited onto magnetic or
paramagnetic metal oxide particles and utilized in the emanation
source. Various methods can be utilized to sorb or deposit the
source isotopes onto the support in the emanation source such as by
electrolytic deposition or by introduction of source isotopes
and/or particles in fluids and particle suspensions, for example.
Radioactive gaseous daughter or granddaughter isotopes generated by
the source isotopes in the emanation source can include radon (Rn)
isotopes such as Rn-219; Rn-220; Rn-222, and radioactive noble
gases such as radioactive xenon isotopes and radioactive krypton
isotopes. The radioactive gas is transported out of the emanation
source out of the emanation generator separating the radioactive
gas from the source isotope. The radioactive gas can be captured
and collected by a collection device and retained for a time
sufficient to allow decay of the radioactive gas to yield one or
more high-purity daughter isotopes. Radioactive daughter isotopes
depend on the source isotopes that are utilized. Radioactive
daughter isotopes can include Pb-212, Bi-212, Pb-211, Bi-211,
Pb-214, Bi-214, and combinations of these daughter isotopes.
Daughter isotopes can also comprise radioactive xenon isotopes,
radioactive krypton isotopes or other radioactive noble gases.
These daughter isotopes can be utilized, for example, as
therapeutic isotopes in radiotherapeutic applications. The
collection device can include a cooling device configured to cool
the radioactive gas emanated from the emanation device. The
collection device can also include a cryogen such as liquid
nitrogen or dry ice bath. The collection device can also include a
capture material or sorbent comprised of a soluble salt configured
to sorb the radioactive gas emanated from the emanation device
therein. The soluble salt may be introduced as a thin film or a
packed salt. Soluble salts can include soluble organic salts such
as urea; soluble inorganic salts including buffer salts such as
acetate buffer salts, carbonate/HEPES buffer salts, and
physiological saline, or other soluble capture materials. In some
embodiments, the capture material can be a thin film comprised of a
lipophilic liquid such as a long-chain hydrocarbon included
dodecane, for example, that extracts the radioactive gas emanated
from the emanation device therein. Alternatively, in some
embodiments, the capture material can be a lipophilic liquid coated
onto solid supports such as metal or resin beads. The collection
device can also utilize a combination of cooling or cryogenic
temperatures along with various capture materials described herein.
The system can also include an eluent delivery device or system
configured to deliver fluids through the collection device to
recover the radioactive daughter isotopes such as biologically
compatible aqueous solutions, for example. Radioactive daughter
isotopes include Pb-212 and/or Bi-212; Pb-211 and/or Bi-211; and
Pb-214 and/or Bi-214 including daughter isotopes thereof.
[0006] In operation, the process can include emanating a
radioactive gas generated from a source isotope within a source
material to separate the radioactive gas as a pure product. Then,
the separated radioactive gas can be collected and retained for a
time sufficient to decay the radioactive gas to yield one or more
high purity radioactive daughter isotopes. For example, Ra-224
isotopes from a legacy source can be utilized by introducing the
Ra-224 isotopes into the emanation source which can then be mounted
into a housing or other device framework to form the radon (e.g.,
Rn-220) emanation generator. Then, Rn-220 generated by the Ra-224
source material is emanated from the emanation generator separating
the gaseous Rn-220 from the Ra-224 isotopes in the emanation source
providing a single gas-phase Rn-220 isotope in the generator.
Rn-220 gas separated from the emanation generator is then captured
in a collection system or device where the gas is retained while
the captured gas decays to form non-gaseous daughter isotopes
Pb-212 and/or Bi-212 that accumulate in the collection device and
can be recovered from the collection device in a pure state for use
as radiotherapy isotopes. However, embodiments of the disclosure
are not intended to be limited. For example, source isotopes with
any decay chain that passes through (Rn) gas that forms (Rn)
daughters can be purified as described herein. Exemplary source
isotope systems include Thorium-228 and/or Radium-224; Thorium-227
and/or Radium-223; or Thorium-230 and/or Radium-226. Radioactive
gases can include Radon-220; Radon-219; and Radon-222. Gaseous
isotopes that decay through other noble gas elements such as xenon
and krypton may also be utilized. Exemplary radioactive daughter
isotopes include Pb-212 and/or Bi-212; Lead-211 and/or Bismuth-211;
and Lead-214 and/or Bismuth-214 and daughter isotopes thereof. The
collecting step can include cooling the emanated radioactive gas
with a cooling device or cryogen to condense or deposit the
emanated radioactive gas. The collecting step can also include
extracting the radioactive gas on a thin film or a packed column
comprised of a soluble salt; or in a thin film or thin film coating
comprised of a lipophilic material on a solid support. Then,
recovering the radioactive daughter isotopes can be performed
utilizing a fluid such as a biologically-compatible aqueous
solution. This system and approach can also eliminate need for
complex aqueous radiochemical processes including, for example,
precipitation, solvent extraction, and column separations utilized
in the prior art requiring intense thermal heating to separate,
distill, and recover product isotopes. For example, isotope
production generators in the prior art do not separate (Rn)
generated by the source isotope but allow radon to decay in
fluid-filled static columns which are known to have breakthrough
problems by containing high-level isotopes in these separation
columns. Isotope production and purification of the instant
disclosure utilizes separation of radon gas from the source isotope
thus reducing need for labor-intensive steps utilized in the prior
art to generate production isotopes.
[0007] The purpose of the foregoing abstract is to enable the
United States Patent and Trademark Office and the public generally,
especially the scientists, engineers, and practitioners in the art
who are not familiar with patent or legal terms or phraseology, to
quickly determine the nature and essence of the technical
disclosure of the application. The abstract is neither intended to
define the invention of the application which is measured by the
claims nor is it intended to be limiting as to the scope of the
invention in any way. Various advantages and novel features of the
present invention are described herein and will become further
readily apparent to those skilled in this art from the following
detailed description. In the preceding and following descriptions
preferred embodiments of the invention contemplated for carrying
out the invention will be shown. As will be realized, the invention
is capable of modification in various respects without departing
from the invention. Accordingly, the drawings and description of
the preferred embodiments set forth hereafter are to be regarded as
illustrative in nature, and not as restrictive. The present
invention covers all modifications, alternative constructions, and
equivalents falling within the spirit and scope of the invention as
defined in the claims. Therefore the description should be seen as
illustrative and not limiting.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] FIGS. 1A-1B illustrate one embodiment of a radon emanation
system and process for production of high purity therapeutic
isotopes.
[0009] FIGS. 2A-2F show different emanation generators and methods
for preparing same.
[0010] FIGS. 3A-3C show exemplary gas capture and collection
devices.
[0011] FIGS. 4-5 show different radon collection results.
DETAILED DESCRIPTION
[0012] A production system and process are disclosed for producing
high purity isotopes for therapeutic applications that address
well-known problems in prior art isotope generators including
eliminating breakthrough by high energy isotopes that contaminate
the recovered product. In the following description, embodiments of
the present invention are shown and described by way of
illustration of embodiments contemplated and various
implementations of embodiments of the disclosure. It will be clear
from this description that the invention is not limited to these
illustrated embodiments but that the invention also includes a
variety of modifications and alternative constructions and
embodiments thereof. It will be clear from the following
description that the invention is susceptible of various
modifications and alternative constructions. While the invention is
susceptible of various modifications and alternative constructions,
it should be understood that there is no intention to limit the
invention to the specific forms disclosed, but, on the contrary,
the invention is intended to cover all modifications, alternative
constructions, and equivalents falling within the spirit and scope
of the invention as defined in the claims. Therefore the
description should be seen as illustrative and not limiting.
[0013] FIGS. 1-5 show different embodiments of a system and
processes for production of high purity isotopes and results
demonstrating their effectiveness. The disclosure is not intended
to be limited to any specific isotope as the system and processes
can be configured for production of other high purity isotopes
detailed further herein. Referring first to FIG. 1A, one embodiment
of an exemplary isotope production system 100 for production of
high purity isotopes 26 for therapeutic applications is shown such
as, for example, Pb-212 and/or Bi-212. System 100 includes an
emanation generator 2 that includes an emanation source 4 loaded
with a source isotope 6. Emanation generator 2 is configured to
automatically separate radon generated in the emanation source 4
from other isotopes therein by releasing radon gas 10 as a pure gas
or in a carrier gas which generators in the prior art do not do
thus enabling various isotope sources to be utilized in the
emanation source 4 including, for example, less purified source
isotope mixtures 6 and even lower-grade sources which reduces
expense and simplifies production of recovered high purity isotopes
26 therein. In one exemplary embodiment, emanation generator 2 can
include an emanation source 4 loaded with, for example, a source
isotope 6 configured to generate Rn-220 gas 10, for example.
Exemplary sources include, for example, a single isotope as well as
combinations of isotopes. In some embodiments, the source isotope
is a single Ra-224. In other embodiments, source isotopes 6
including long-lived radioisotopes and combinations of these
isotopes may also be utilized including, for example, Th-228 and/or
U-232, that in prior art generators are problematic. For example,
emanation generator 2 is preferably constructed of non-lipophilic
materials such as stainless steel that are not subject to
radiolytic breakdown as in the prior art so as to not be affected
by the emanation gas 10 transported from emanation source 4. These
materials are radiolytically stable in prolonged contact with alpha
(.alpha.) and beta (.beta.) particles emitted by the source isotope
6 therein and enabling the radon (Rn) gas to be generated and
delivered at a sustainable and high Rn emanation power which
addresses another known problem in prior art generators that
utilize lipophilic materials to contain the source isotope which
can reduce emanation power in these prior art generators. However,
even if radiolytically susceptible source materials 4 are utilized,
these emanation source materials can be exchanged before radiolytic
breakdown can even take place. Emanation source 4 also does not
require high-purity source isotopes to be utilized as in prior art
generators that generally require high-purity and single source
isotopes to be utilized with the generally involved separation and
purification of these source isotopes.
[0014] In some embodiments, emanation source 4 containing source
isotopes 6 can be arranged, for example, as a column or stack of
isotope-bearing membranes, screens, filters, and porous discs that
enables a greater quantity of the source isotope 6 or a more
dispersed source isotope 6 to be assembled within a fixed diameter
or geometry in emanation generator 2 to provide a maximum emanation
power for generating the emanation gas 10.
[0015] In the exemplary embodiment, radon emanation generator 2
containing the installed Ra-224 (and Rn-220 producing) emanation
source 4 provides efficient emanation and delivery of the Rn-220
emanation gas 10 at a high Rn-220 emanation power. Emanation power
(E) for Rn-220, for example, is given by the ratio of the activity
of the Rn-220 and any of its resulting daughter isotopes collected
in the collection stage 24 to the activity of the Ra-224 source
isotope 6 in the emanation source 4. An emanation power greater
than or equal to about 60% is preferred and more preferably greater
than or equal to about 90%.
[0016] System 100 has a modular design in which emanation source 4
containing the source isotope (generation nuclide) 6 is positioned,
for example, within a housing 8 or other assembly whereby the
emanation generator 2 can be readily decoupled from the collection
device 24 enabling the emanation generator 2 and/or source isotope
6 to be replaced or exchanged with a same or different emanation
generator 2 and/or source isotope 6 due to the finite lifetime of
isotope source 6 due to radioactive decay. Exchange or replacement
of isotope source 6 or emanation generator 2 enables emanation
source 4 to provide a maximum radon emanation power without reduced
production of resulting high-purity product isotopes. Modularity of
emanation generator 2 and emanation source 4 addresses well-known
problems of radiolytic breakthrough in prior art generators by
enabling exchange of the emanation device 2 and/or emanation source
4.
[0017] In one exemplary embodiment, housing 8 can comprise two
metal disks 12 constructed of corrosion-resistant stainless steel,
for example. A valve 14 coupled to housing 8 can be utilized to
introduce a carrier gas 1 through emanation source 4, and emanation
generator 2, for example. An outlet valve 16 can be utilized to
deliver separated emanation gas 10 out of emanation source 4 and
away from emanation generator 2, for example. In some embodiments,
several emanation devices 2 and collection devices 24 can run in
tandem or parallel to maximize process efficiency utilizing
respective eluent delivery systems 36 to provide optimal recovery
of product isotopes 26 for maximum collection yields. In some
embodiments, an eluent delivery system 36 such as a switchable
valve system can be utilized to deliver a single eluent 37 to the
collection device 24 to maximize efficiency of isotope recovery of
radon decay products 26. In other embodiments, the eluent delivery
system 36 can include a digital syringe pump or other fluid
dispensing devices, for example, with output lines connected to
inlet valve 16 that deliver eluents 37 into the collection assembly
24 for recovery of product isotopes 26, for example. The trap 24
outlet 18 can be connected to various collection systems 26 and
devices 26 including fraction collectors and septa vials, for
example. Eluent delivery system 36 can deliver various eluent
solutions 37 and volumes at various flow rates, for example.
Elution profiles of the Pb-212 can be determined and charted, for
example, by counting each collected elution fraction with a gamma
detector. Various computer-controlled devices can be utilized to
automate components or devices within system 100 to automate any
suitable aspect of isotope production and to provide consistent
production results in each production cycle. Automation also
enables higher-activity sources behind shielding to be utilized
thereby minimizing radiologic handling doses. System 100 can also
include a scrubber system 22 configured, for example, to remove any
non-collected radon-derived isotopes that might reside, for
example, in the carrier gas 1 before releasing carrier gas 1 from
the system 100 or recycling the carrier gas 1 for reuse. Activated
charcoal or similar materials installed in a scrubber 22 provide
high scrubbing efficiency for radon, for example.
[0018] System 100 can also include a collection device or system 24
that captures emanation gas 10 released from emanation generator 2.
The emanated Rn-220 gas 10 undergoes radioactive decay in the
collection system 24 for a time sufficient to form pure Pb-212
and/or Bi-212 product isotopes 26 (see FIG. 1B) that accumulate in
a pure state therein. After collection, these isotopes can be
eluted from the collection system 24, for example, with a
biologically-compatible aqueous solution such as physiological
saline or other pH neutral eluent solutions, for example, that are
compatible with proteins utilized for isotope labeling, for
example. These eluent solutions 37 enable product isotopes 26 to be
recovered and directly utilized for therapeutic treatment and/or
diagnostic imaging, for example. Other biologically-compatible
eluent solutions may be utilized including, for example, isotonic
solutions, buffered solutions such as acetate buffers;
carbonate/HEPES buffer solutions; urea solutions; and combinations
of these various solutions. Biologically-compatible eluents can
eliminate need for high concentration acidic solutions such as
hydrochloric or other acids and other involved wet chemistry and
process steps that in the prior art are required to convert
chemical matrices of recovered isotopes. For example, prior art
systems and approaches generally require acidic solutions as
eluents to recover product isotopes and thereafter heating to
remove these unsuitable chemical matrices by evaporation with
re-dissolution of dried residual salts in an appropriate labeling
solution. Alternatively, prior art systems require addition of
buffering agents to the eluted isotope products to bring pH to an
appropriate level for labeling. Each step adds time, labor, and
materials costs to processing. These biologically-compatible
solutions enable quantitative elution and recovery of the Pb-212
and/or Bi-212 product isotopes 26 from collection system 24 with
minimal to no processing after recovery. For example, as shown in
FIG. 1B, eluents 37 can be introduced into the capture device 24,
for example, by opening an inlet valve 16 leading into the capture
device 24 enabling the eluent 37 to flow through the capture device
24 to recover product isotopes 26 formed therein. Eluted product
isotopes can be recovered, for example, by opening an outlet valve
18 positioned, for example, at the releasing end of the collection
device 24 enabling eluted product isotopes 26 to be recovered
(e.g., periodically) from the collection system 24 for intended
therapeutic applications, for example. Various valves and valve
systems or tees can be utilized for introducing carrier gases and
eluents into and out of various devices and/or processing stages
within system 100 at various processing points. As such, number and
position of valves and valving systems and tees are not intended to
be limited.
[0019] In one exemplary approach for preparing emanation source 4
shown in FIG. 2A and FIG. 2B, a quantity of solid sorbent particles
40 containing source isotopes or generator nuclides 6 adsorbed on
the surfaces of sorbent particles 40 can be introduced through an
inlet valve 14 as a suspension 43 suspended in a carrier fluid 17
or source 6 liquid 17 and collected with a permeable support 41
such as by sorption or deposition with a filter 41 that forms
emanation source 4. Filtrate 46 can be recovered. Other methods can
also be utilized as described further herein.
[0020] In another exemplary approach shown in FIG. 2C and FIG. 2D,
a solution 17 containing the source isotope 6 can be delivered, for
example, through the inlet valve 14 in emanation generator 2 and
collected such as by sorption or deposition on surfaces of sorbent
particles 40 that are supported on a preassembled membrane 41 such
as a permeable metal membrane, screen, or filter that forms
emanation source 4. Filtrate liquid 46 can be recovered. In some
embodiments, sorbent particles 40 can be high surface area metal
oxide particles such as iron magnetite (Fe3O4) particles or other
particles with chemistries that provide a high adsorption
coefficient for preferential collection and retention of source
isotopes 6 on surfaces of these particles 40 in emanation source 4.
Particles 40 can be magnetic or paramagnetic or even
chemically-modified magnetic or paramagnetic particles 40.
[0021] In another exemplary approach shown in FIG. 2E and FIG. 2F,
a carrier liquid 17 containing sorbent particles 40 such as
magnetic or paramagnetic nanoparticles 40 with source isotopes 6
sorbed thereon can be delivered, for example, as a particle 40
suspension 43 through inlet valve 14 for collection on a porous
metal support 41 such as a metal frit or metal filter or a metal
screen filter while applying a magnetic field to the metal support
41 utilizing a magnet 44, for example, to collect the metal
particles 40 on the surface of the metal support 41 while allowing
filtrate liquid 46 to pass through the metal support 41 for
collection. Then, the filter 41 containing the captured particles
40 can be dried to form the emanation source 4 introduced into the
emanation generator 2 prior to operation. Other approaches can also
be envisioned such as evacuating the carrier liquid 17 and
transferring the particles, or by, for example, removing the
magnetically aggregated particles 40 from the source 6 liquid by
evacuation through a directly coupled metal support 41 coupled to
an evacuation line. Other collection methods are also envisioned.
For example, system 100 can be easily configured for loading source
isotopes 6 into emanation source 4 through inlet valve 14 as
described, for example, and then configuring the system 100 for
capture of Rn gas 10 as described herein.
[0022] In another exemplary approach, the source isotope 6 can be
deposited onto an emanation source 4 by deposition methods such as
electrodeposition, for example. A gas-permeable filter, screen, or
porous disc 41 may be utilized having suitable conducting
properties that enable functioning as an electrode when placed in
the electrodeposition chamber. Then, when immersed in an
appropriate electrolyte solution containing the source isotope 6 at
an appropriate voltage potential or current condition, the source
isotope 6 can be electrolytically deposited onto the surface of the
gas-permeable filter, screen, or porous disc 41. Upon removal from
the electrolyte solution depleted of source isotope 6, the
gas-permeable filter, screen, or porous disc 41 now loaded with the
source isotope 6 can form an emanation source 4 that can be
utilized in an emanation generator 2.
[0023] In some embodiments, gas collection system 24 can be coupled
to a vacuum device 20 as shown in FIG. 3A that is configured to
pull the emanation gas 10 released from the emanation generator 2
into the collection device 24 for capture of the emanation gas
therein. In the instant embodiment, collection device 24 can
include a tube 24 constructed of a suitable material such as
corrosion resistant stainless steel, for example, with a convoluted
or serpentine shape to increase the surface area for collection of
the emanation gas 10 therein. Tube 24 has a sufficient length, for
example, to retain captured radon gas 10 and allow decay into the
Pb-212 and/or Bi-212 isotope daughter products therein which can be
recovered as described above.
[0024] In another embodiment shown in FIG. 3B, collection device 24
can include a capture material 25 such as a sorbent introduced, for
example, as a thin film 25 onto an inner wall 38 that captures
radon gas 10 by extraction, sorption, or deposition when
transported from emanation generator 2. The capture material 25 may
be include soluble inorganic salts such as buffer salts and
physiological salts; organic salts such as urea; and soluble
organic proteins such as gelatins that extract the emanation gas 10
in the thin film 25, as shown. In some embodiments, the thin film
capture material 25 can be comprised of lipophilic materials
including long-chain hydrocarbons such as dodecane, for
example.
[0025] Collection device 24 can also be cooled with cooling devices
34 as shown such as thermoelectric cooling devices (e.g., Peltier
devices); chilled fluid delivery devices; Dewar devices filled with
liquid cryogens such as liquid nitrogen or dry ice bath; gas traps;
and cooled adsorption devices. As shown in the figure, the
collection device 24 is encompassed within the cooling zone 35 to
enhance capture of the emanation gas 10 in the collection device
24. These cooling devices enable the emanation gas 10 to condense
within the collection device 24 enabling the radon gas 10 to be
captured at a temperature at or near the cryogenic temperature, for
example. In one example, emanated radon gas 10 can be collected,
for example, by cooling the collection tube 24 in a cooling zone 35
filled with liquid nitrogen or a dry ice bath and condensing the
gas 10 at a temperature at or near the cryogenic temperature, for
example. In another example, the collection device 24 can be
immersed into a Dewar type cooling vessel 34 containing a liquid
cryogen as cooling zone 35 enabling radon gas 10 introduced through
the collection tube 24 to be condensed or deposited and captured
therein. Decay of the captured emanation gas 10 can then be allowed
to take place to form the daughter products 26 as described
previously above. In another embodiment shown in FIG. 3C,
collection device 24 can also be filled or packed with the radon
capture sorbent 25 such as with the soluble inorganic or organic
capture salt to completely capture the emanation gas 10 in
collection device 24. In some embodiments, the thin film capture
material 25 can be comprised of lipophilic materials coated on a
solid support such as a metal or resin bead.
[0026] Collection device 24 can also be coupled to a cryogenic
cooling device 34 or cryogen 34, for example, to encompass the
cooling device and capture material 25 in a cooling zone 35 to
enhance capture of the emanation gas 10 in the collection device
24. Cooled surfaces 38 and/or capture materials 25 within the
collection device 24 can be warmed, for example, to a temperature
such as room temperature to facilitate collection of accumulated
product isotopes 26 such as Pb-212 and/or Bi-212 daughter 26 at a
high purity via elution. Collection of the daughter isotopes 26 can
be performed, for example, by removing the collection device 34
from the cooling zone 35 to warm the collection device 24 and/or
the capture material 25 enabling collection of the product isotopes
26 utilizing an eluent 37 delivered from an eluent delivery system
36, for example.
[0027] Upon introduction of the eluent solution 37 into the
collection tubing 24 or packed column 24, the soluble capture salt
or protein 25 that retains the product isotopes becomes soluble in
the eluent solution 37 which dissolves the capture salt or packed
salt 25 to release the retained product isotopes into solution
enabling recovery of the product isotopes 26 in the eluent solution
37. Alternatively, the eluent solution 37 can act in a solvent
extraction process to remove isotope products 26 from lipophilic
thin films 25 or lipophilic coatings 25 on metal or resin beads,
for example.
[0028] Various combinations of these different configurations and
embodiments can also be utilized. Purity of the eluted isotope
products 26 is high with chemical yields preferably greater than or
equal to about 60% and more particularly greater than or equal to
about 90%.
[0029] In preferred embodiments, cooling device 34 can be utilized
as a switchable cold source that in cooling mode condenses or
deposits the emanation gas 10 onto the capture material 25 enabling
capture and collection of the radioactive gas 10 in the cooled
collection device 24. In addition, switching between cooling and
warming modes can be activated remotely, for example, via computer
enabling effective capture during the cooling cycle and elution of
daughter isotopes 26 during the warming cycle. Various alternative
approaches are also envisioned.
Example 1
[0030] One embodiment of an isotope production system was utilized.
Cryogenic capture of Rn-220 gas via deposition from a carrier gas
stream was demonstrated. A gas flow assembly was utilized having a
gas emanation source loaded with .about.50 kBq Th-228/Ra-224
isotope mixture that was sorbed onto 1 mg of magnetite (Fe3O4)
particles that were chemically modified to include MnO2 (e.g.,
forming Mn-doped Fe3O4). Particles were collected on a gas
permeable syringe filter disc forming a radon emanation source that
was then coupled atop a coiled stainless steel tube. The tube
outlet was connected to a scrubber filled with activated charcoal
to collect and provide quantitative capture of any Rn-220 gas
released through the coiled tube. The coiled tube was configured to
be immersible into a 1 L Dewar filled with liquid nitrogen while
the activated charcoal scrubber remained positioned outside the
cooling zone. FIG. 4 presents radiological counting (activity)
results for Rn-220 gas in the activated charcoal trap both with and
without cryogenic cooling. At room temperature, capture results
show that Rn-220 gas was delivered through the coiled tube and
captured in the activated charcoal trap. Cryogenic cooling results
show Rn-220 gas from the emanated gas stream was quantitatively
deposited and captured in the coiled stainless steel tube; no
Rn-220 was delivered to the activated charcoal trap.
Example 2
[0031] The emanation source of Example 1 was utilized. Rn-220 gas
was captured onto a column packed with a soluble salt comprised of
solid urea powder utilizing a phase change induced by cryogenic
cooling and physisorption. The column packed with urea powder was
connected between the emanation source and a scrubber containing
activated charcoal therein. The packed column was immersed in a
Dewar containing liquid nitrogen and carrier gas was then delivered
through the system. The collection column was removed from the
cryogen after .about.2 days and Pb-212 product isotopes resulting
from Rn-220 decay were detected with a gamma detector to establish
activity on the column. 5 mL of physiological saline were then
delivered through the column to dissolve the urea powder to recover
the Pb-212 product isotopes captured therein. Residual activity
within the column after urea salt was removed was again measured by
the gamma detector. FIG. 5 shows the Pb-212 activity before and
after elution of the column with physiological saline. Preliminary
results showed that .about.87% of the Pb-212 originally in the
column was recovered from the column when the urea capture salt was
dissolved by physiological saline. Further optimization is expected
to increase recovery.
[0032] While a number of embodiments of the present invention have
been shown and described, it will be apparent to those skilled in
the art that many changes and modifications may be made without
departing from the invention in its broader aspects. The appended
claims are therefore intended to cover all such changes and
modifications as fall within the scope of the invention.
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