radioisotope production capabilities at mcmaster university
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Defence Research and Development Canada Contract Report DRDC-RDDC-2021-C147 July 2021
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Radioisotope Production Capabilities at McMaster University
Andrea Armstrong, PhD McMaster Nuclear Reactor Prepared by: Nuclear Operations & Facilities McMaster University, NRB 225 1280 Main St. West Hamilton, ON L8S 4K1 PSPC Contract Number: W7702-4502142672 Technical Authority: Tim Munsie, Defence Scientist Contractor's date of publication: February 2021 Terms of Release: This document is approved for public release. The contents of this Contract Report do not contain the required security markings according to DND security standards; however, the report itself must be protected appropriately based on the assigned security markings noted on the cover and the terms and conditions specified in the statements above.
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Radioisotope Production Capabilities at McMaster University
Prepared for Dr. Tim Munsie DND Contract No. W7702-4502142672 Defence Scientist Defence Research & Development Canada Building 560 Mount Sorrell Road Ralston, AB T0J 2N0 CANADA
Prepared by Andrea Armstrong, PhD. Research Scientist Nuclear Operations & Facilities McMaster University, NRB 225 1280 Main St. West Hamilton, ON L8S 4K1
February 28, 2021
1
Abstract/Résumé McMaster University is a world leader in radioisotope production. It is the only site in Canada that can make both cyclotron- and nuclear reactor-generated radioisotopes. Nearly 100 different radioisotopes can be generated at McMaster University, with lead times ranging from 1-2 weeks to several months. The cost and purity of each radioisotope depends on the precise conditions used to generate it. L’Université McMaster est un leader mondial de la production de radio-isotopes. C’est le seul site au Canada qui peut produire à la fois des radio-isotopes générés par des cyclotron et des réacteurs nucléaires. Près de 100 radio-isotopes différents peuvent être produits à l’Université McMaster, avec des délais allant de 1 à 2 semaines à plusieurs mois. Le coût et la pureté de chaque radio-isotope dépendent des conditions précises utilisées pour la générer.
2
1. Introduction to McMaster University
McMaster University is one of Canada’s most research-intensive universities, and consistently ranks among the top 100 universities in the world. Nuclear science and engineering is a particular strength at McMaster: the university campus is home to a unique suite of world-class nuclear research facilities that enable discoveries in clean energy technology, medicine, advanced materials, nuclear safety, and environmental science.
The university’s five complementary nuclear facilities are anchored by the 5 MW McMaster Nuclear Reactor (MNR), which is Canada’s only major neutron source; it serves as a source of neutrons for radioisotope production and a variety of research applications. The Centre for Advanced Nuclear Systems is a post-irradiation examination facility for analyzing highly radioactive materials including in-service components from Canada’s nuclear power plants. The High Level Laboratory Facility is a 24,000 square foot laboratory space that is licensed and equipped for processing open sources of radioisotopes. The McMaster Accelerator Laboratory houses three particle accelerators and a large volume gamma irradiator. Finally, the McMaster University Cyclotron Facility (MUCF) comprises a 16 MeV medical cyclotron and a suite of hot cells for manufacturing clinical-grade radiopharmaceuticals.
This combination of infrastructure gives McMaster University unique-in-Canada capabilities in radioisotope production. The co-location of the university’s nuclear reactor and cyclotron enables generation of both neutron-rich and proton-rich radioisotopes, giving McMaster nearly universal production capabilities. Radioisotopes can be processed, purified, and analyzed for purity in the university’s laboratory facilities to meet stringent quality standards. Finally, the presence of hot cells in conjunction with both the reactor and cyclotron allows McMaster University to produce and ship bulk (TBq) quantities of radioisotopes to support a wide variety of applications.
2. Radioisotopes in Routine Production
McMaster University is currently the world’s leading supplier of two medical radioisotopes – iodine-125 and holmium-166 – and also provides routine dispensing of lutetium-177.
Iodine-125 (I-125) is dispensed weekly as an aqueous (sodium hydroxide) solution in TBq quantities. This product is manufactured with full process controls to meet the quality assurance standards required by the medical device manufacturing sector. Unlike the iodine-125 produced at some other facilities, the product supplied by McMaster University does not contain any traces of long-lived cesium radioisotopes.
Holmium-166 is generated in multi-GBq quantities at McMaster University in a medical device known as QuiremSpheres. These microscopic polymer beads are used to immobilize the radioisotope, which can then be implanted locally by physicians to treat liver cancer and related conditions. This product is supplied exclusively to Qurirem Medical, and is not available to third parties through McMaster University.
Lutetium-177 is produced at McMaster University on a triweekly basis from enriched lutetium-176 targets. The isotope is dispensed as an aqueous (hydrochloric acid) solution in quantities up to 5 GBq, and is dispatched with a certificate of analysis indicating radionuclidic purity and specific activity (see Table 1).
McMaster University is currently scaling up a process developed in-house to generate no carrier added (n.c.a.) lutetium-177 from enriched ytterbium-176 targets. The lutetium-177 produced from this process contains neither traces of the long-lived by-product lutetium-177m (t½ = 160 d), nor residual non-radioactive lutetium-176. This product will become available routinely (as an aqueous solution) in the 4th quarter of 2021.
3
The McMaster University Cyclotron Facility has served as a major regional supplier of the fluorine-18 radiopharmaceutical FDG for nearly a decade. As of January 2021, the cyclotron has been rededicated to research and development, rather than clinical production. Staff scientists at McMaster are working to develop a utilization plan for this facility. The cyclotron is scheduled to reinstitute routine production of fluorine-18 as aqueous sodium fluoride (Na18F(aq)) in the Fall of 2021 to support research activities.
Table 1. Radioisotopes in routine production at McMaster University.
Isotope Half-life Decay
product Production
route Radionuclide
impurities Specific activity
Availability
Fluorine-18 (F-18)
109 min O-18 18O(p,n)18F tbd No carrier
added Weekly
(Fall 2021)
Iodine-125 (I-125)
59.4 d Te-125 124Xe(n,γ)124Xe
→ 125I N/A
No carrier added
Weekly
Lutetium-177 (Lu- 177)
6.7 d Hf-177 176Lu(n,γ)177Lu Lu-177m, <0.01%
≥ 50 GBq/mg Triweekly
Lutetium-177 (Lu- 177, n.c.a.)
6.7 d Hf-177 176Yb(n,γ)177Yb
→ 177Lu N/A
No carrier added
Monthly (Fall 2021)
3. Radioisotope Production Capacity at MNR
The McMaster Nuclear Reactor (MNR) was designed as a multi-purpose research facility that is capable of supporting nearly two dozen research and production activities at any one time. Radioisotope production can be done in any of MNR’s three pneumatically driven irradiation systems, three large-volume irradiation sites, or eight “capsule” positions which include the reactor’s high flux Central Irradiation Facility. These three types of sites can accommodate different sizes of “irradiation targets” and vary in neutron flux as indicated in Table 2. The reactor typically operates at a power output of 3 MW but may be operated at any power between 2 MW and 5 MW depending on demand. Neutron flux scales linearly with operating power, so the flux in a site that experiences 5 x 1012 n/cm2·s at 3 MW would experience 8.3 x 1012 n/cm2·s at 5 MW, for example.
Table 2. Neutron irradiation facilities at MNR (fluxes at 3 MW).
Pneumatic systems
Capsules Central Irradiation
Facility Large Volume
Neutron flux (n/cm2·s)
5 x 1012 8-22 x 1012 70 x 1012 1-10 x 1012
Maximum sample dimensions
8 x 25 mm 16 x 75 mm 16 x 75 mm 6 x 75 cm
12 x 75 cm
Maximum irradiation time
60 min N/A N/A N/A
4
The university’s operating license for MNR is flexible and does not stipulate which radioisotopes can or cannot be produced in-core. In consequence, additional permits or licensing from the Canadian Nuclear Safety Commission are generally not required to generate a given radioisotope, even if it has not been done previously at McMaster. However, any “irradiation target” that is placed in the reactor core (Figure 1) to generate a radioisotope must conform to MNR’s stability and encapsulation requirements.
Figure 1. The layout of the MNR core with sample sites marked (left); photo of reactor core (right).
To be considered suitable for neutron irradiation in the McMaster Nuclear Reactor, samples must exhibit high thermal stability (melting point ≥ 300 °C, decomposition temperature ≥ 500 °C) and low chemical reactivity toward air and moisture. Materials that are capable of nuclear fission or have abnormally large neutron capture cross-sections must be evaluated by the Reactor Manager prior to approval for irradiation. A list of specific substances that are banned from in-core irradiations can be obtained from Nuclear Operations & Facilities upon request.
All samples irradiated at MNR must be double-encapsulated to prevent contact with reactor systems or pool water. For pneumatically driven systems, samples are provided to end users in heat-sealed cylindrical polyethylene vials (8 x 25 mm); these vials can also be used for short (≤ 4 h) in-core irradiations. For longer irradiations, samples are prepared in quartz tubes (6-8 mm x 60 mm) with a fitted quartz cap and wrapped in aluminum foil. If necessary, multiple quartz tubes can be placed with a single capsule or large volume site, and as many as three capsules can be placed in one irradiation site.
In contrast to radioisotopes in routine production at McMaster University (see Section 2), which are chemically processed, analyzed, and dispatched as solutions, most radioisotopes produced on-demand at MNR are shipped in their original irradiation containers without further analysis. These technical grade radioisotopes may contain radioactive impurities due to incidental activation of trace impurities in the irradiation target: this can be minimized but not always avoided completely by sourcing high purity (99.999%+) chemicals to use as targets, and avoiding the use of sulfate or phosphate salts. Another source of impurities is neutron activation of other stable isotopes within the high purity target; if this is problematic, a target that is enriched in the stable isotope of interest can be procured at additional cost and used in place of natural abundance material. Finally, though the neutron flux at MNR is largely thermalized, side reactions can occur due to epithermal or fast neutron reactions on the irradiation target. This is only problematic for certain chemical elements; if it is of concern for a particular target, a site with
5
a low proportion of highly energetic neutrons can be used.
For applications where radionuclidic purity is critical, research staff at McMaster can conduct a trial irradiation followed by a full characterization of radioactive impurities after the bulk radioisotope has decayed. If necessary, chemical processing can also be done to separate out radioactive impurities. Depending on the scale at which the radioisotope is produced, developing a purification method can require several months of scale-up, as work must follow the Canadian Nuclear Safety Commission’s standard permitting system, with incremental progress from the Basic to Intermediate to High Level, as necessary.
4. Radioisotope Production Costs at MNR
The cost of producing a radioisotope at the McMaster Nuclear Reactor is determined by the cost of materials (irradiation target, encapsulation supplies), labour (capsule preparation and testing, targetry development, safety or engineering analysis), and irradiation site occupancy.
However, it is not possible to create a precise price list for MNR-generated radioisotopes without detailed information about the mass and chemical form of the target, the required specific activity (Bq/g), and the tolerance on radionuclidic impurities. For example, a radioisotope that can be produced from a 1 hour irradiation of a 1 g target in capsule 8C could also be produced from a 10 hour irradiation of a 0.1 g target: in both cases the same 1 GBq is produced, but the specific activity differs by a factor of ten, as does the cost of the irradiation site occupancy. Add to this the wide variation in sample sizes and neutron fluxes at MNR, and it becomes apparent that there are multiple possible configurations that can be used to produced the same quantity of any given radioisotope. Moreover, as MNR is capable of producing nearly 100 different radioisotopes, creating a comprehensive price list would be a herculean task.
To create approximate pricing guide for 1 GBq of each of the radioisotopes that can be produced at MNR, a series of assumptions were made and held constant for all production routes indicated in Tables 3-7. First, an irradiation target mass of 1 gram or less was used, as this amount of material can fit inside any of MNR’s irradiation sites. Second, the operating power of the reactor was fixed at 3 MW. Third, a neutron flux of 5 x 1012 n/cm2·s was used for Table 3 only, and a neutron flux of 16 x 1012 n/cm2·s for Tables 4-6; capsule sites with this flux have good availability at MNR, which will minimize lead times. Fourth, it was assumed that no additional analytical work was required prior to or after generation of the radioisotopes: the isotopes would simply be shipped as-is, without a certificate of analysis. Finally, the proposed production routes were grouped together into pricing Tiers based on approximate anticipated costs.
Shipping categories were calculated assuming the use of a Biodex Compact PET Shipping System with a Vial Pig, using gamma constants (R•m2 per Ci•h) from Thomas E. Johnson & Brian K. Birky, Health Physics and Radiological Health, 4th edition (Baltimore: Lippincott Williams & Wilkins, 2012), p 255-282. For certain radioisotopes, the dose rate at the package surface was calculated to exceed the maximum permissible value of 2 mSv/h. In these cases, the 1 GBq of radioisotope would have to be produced in two or more targets that could be packaged into separate Type A containers to ensure compliance with Transportation of Dangerous Goods regulations.
The “Tier 1” radioisotopes that can be generated at MNR are shown in Table 3. These isotopes can be produced at the lowest cost, from standard target materials and the minimum time (1 h) available in MNR’s pneumatic irradiation sites, with a 1-2 week lead time. Due to the short irradiation times, chloride salts were not considered as potential irradiation targets as the formation of Cl-38 (t½ = 37 min) would necessitate ~ 6 h decay prior to shipment. Samples of copper-64 and gallium-72 would be held prior to shipment to allow decay of Cu-66 (t½ = 5 min, 1 h hold) and Ga-70 (t½ = 21 min, 4 h hold), respectively.
6
Tab
le 3
. Tie
r 1
rad
iois
oto
pes
ava
ilab
le f
rom
MN
R (
1 G
Bq
) Is
oto
pe
Ir
rad
iati
on
Ta
rge
t H
alf
-lif
e
De
cay
pro
du
ct
Gam
ma
Co
nst
ant
Pro
du
ctio
n
Ro
ute
P
rob
ab
le
imp
uri
tie
s To
xici
ty
con
cern
s Sh
ipp
ing
Cla
ssif
icat
ion
Sod
ium
-24
(N
a-24
) So
diu
m c
arb
on
ate
or
sod
ium
nit
rate
1
4.9
h
Mg-
24
1.
853
2
3 Na(
n,γ
)24N
a N
/A
N
4 x
Yel
low
III
Man
gan
ese
-56
(Mn
-56)
M
an
gan
ese
(II)
oxi
de,
M
nO
2
2.5
8 h
Fe
-56
0.
858
5
5 Mn
(n,γ
)56 M
n
N/A
N
Ye
llow
III
Co
pp
er-
64
(Cu
-64
) C
op
per
met
al o
r co
pp
er (
II)
oxi
de,
CuO
1
2.7
h
Ni-
64, Z
n-
64
0.1
05
63 C
u(n
,γ)6
4C
u
< 1
pp
m C
o-
60
N
Yello
w II
Gal
lium
-72
(G
a-72
) G
alliu
m o
xid
e, G
a 2O
3
14
h
Ge
-72
1.
350
7
1 Ga(
n,γ
)72G
a G
a-7
0, <
1%
N
2
x Y
ello
w II
I
Ars
enic
-76
(A
s-7
6)
Ars
en
ic (
III)
oxi
de,
A
s 2O
3
26.
4 h
Se
-76
0.
231
7
5 As(
n,γ
)76A
s N
/A
Y (≤
4 G
Bq
/g)
Yello
w II
An
tim
on
y-1
22
(Sb
-12
2)
An
tim
on
y (I
II)
oxi
de,
Sb
2O
3
2.7
2 d
Sn
-122
, Te
-12
2
0.2
57
121
Sb(n
,γ)1
22Sb
Sb
-124
, 2.5
%
N
Yello
w II
I
Lan
tha
nu
m-1
40
(La
-140
) La
nth
anu
m o
xid
e,
La2O
3
40
h
Ce
-14
0
1.1
68
139
La(n
,γ)1
40La
N
/A
N
2 x
Yel
low
III
Pra
seo
dym
ium
-1
42 (
Pr-
142
) Pr
aseo
dym
ium
oxi
de
, P
r 2O
3
19
h
Ce
-14
2,
Nd
-142
0.
028
1
41P
r(n
,γ)1
42Pr
C
e-1
41,
< 1
%
N
Yello
w II
Ho
lmiu
m-1
66
(H
o-1
66)
Ho
lmiu
m o
xid
e, H
o2O
3
26.
8 h
Er
-166
0.
016
1
65H
o(n
,γ)1
66H
o
Ho
-16
6m
, 0
.00
2%
N
Ye
llow
II
Rh
en
ium
-18
8
(Re
-18
8)
Rh
eniu
m m
etal
or
amm
on
ium
per
rhen
-at
e, [
NH
4][
ReO
4]
16.
7 h
O
s-1
88
0.0
43
187
Re(
n,γ
)188
Re
R
e-1
86,
20
%
N
Yello
w II
Irid
ium
-19
4
(Ir-
194)
Ir
idiu
m m
etal
, Ir
19.
3 h
P
t-19
4
0.0
51
193
Ir(n
,γ)1
94Ir
Ir
-192
, 6%
N
Ye
llow
II
7
Possible radioactive contaminants in the Tier 1 isotopes were assessed in several different ways. The presence of trace quantities of cobalt-60 (t½ = 5 y) in copper-64 has been document previously in material produced at MNR, even when ultra-high purity copper (II) chloride or copper (II) oxide targets are used. Radionuclidic impurities in antimony-122, rhenium-188, and iridium-194 are due to the presence of other stable isotopes in natural abundance target materials, and were calculated from the standard neutron activation yield equation. Similarly, activation of natural holmium (100% holmium-165) produces primarily Ho-166 (t½ = 26.8 h), but also small quantities of the long-lived radioisotope holmium-166m (t½ = 1200 y), which has been confirmed experimentally at McMaster. Finally, the anticipated cerium-141 (t½ = 32.5 d) contaminant in praseodymium-142 is due to a fast neutron reaction on the target material; the precise proportion of this radioisotope formed would have to be determined empirically for a particular irradiation site at MNR.
The radioisotopes categorized as Tier 2 materials (see Table 4) would require irradiation in a capsule site, rather than the pneumatic sample transfer systems. (The sole exception is samarium-153, which would be produced in the pneumatic system, but using a costly isotopically-enriched irradiation target.) Irradiation times are restricted to 14 hours, which is currently one operating day for the McMaster Nuclear Reactor. Lead times are typically 1-2 weeks, but may be longer (1-4 weeks) if a special target material has to be procured.
The radioisotopes in Table 3 ship within 24 h of end of irradiation, with three exceptions. Bromine-82 is one of four thermal neutron activation products that arise in natural abundance bromine; a delay time of ≥ 36 h is require between the end of neutron irradiation and packaging for shipment. Rhenium-186 (Re-188, t½ = 17 h) and iridium-192 (Ir-194, t½ = 19 h) both require a 10 day decay period to achieve 99% radionuclidic purity when they are generated from natural abundance elements,
The probable radionuclidic impurities listed for Si-31, K-42, Tm-170, W-187, and Au-198 arise due to fast neutron reactions and are only approximations: confirmatory experiments are required to quantify the exact contributions made by each radioisotope. For samarium-153, the Sm-151 (t½ = 93 y) content will depend on the grade of the enriched target material and can be calculated from the Certificate of Analysis for a particular lot of 152Sm2O3. Radioactive contaminants in Zn-69m and Y-88 are also due to fast neutron reactions but have been verified experimentally. Radioactive contaminants in Br-82, Sb-122, Eu-152, Re-186, Re-188, Ir-192, and Ir-194 are due to thermal neutron activation of other stable isotopes of the target element; their contribution to total activity were calculated based on their natural abundance, or the specified enrichment level, in a given target material.
The Tier 3 radioisotopes listed in Table 5 require neutron irradiation times of more than one operating day (14 h), but no more than one operating week (14 h Monday-Friday), or the use of a costly enriched target that increases the total cost of production beyond a typical Tier 2 radioisotope. Lead times are typically a minimum of 2-3 weeks, or a maximum of 8-10 weeks, depending on target availability and irradiation duration. If the MNR operating schedule were to change to a 24 h model, total activation times for some of the shorter-lived radioisotopes would decrease, as less activity would be lost through decay during multi-day neutron irradiations.
The production of phosphorus-32 is complicated by the properties of phosphate salts. Elemental phosphorus is not suitable for irradiation at MNR due to its reactivity toward water; ammonium salts of phosphate are thermally unstable; alkali metals, which form thermally stable salts with phosphate, tend to undergo thermal neutron activation, resulting in unwanted radionuclidic impurities such as sodium-24 (t½ = 14.9 h) and potassium-42 (t½ = 12.4 h). Phosphorus-32 can be generated in good radionuclidic purity as a magnesium pyrophosphate salt, but the target material is not commercially available and would have to be generated in-house at McMaster University.
8
Tab
le 4
. Tie
r 2
rad
iois
oto
pes
ava
ilab
le f
rom
MN
R (
1 G
Bq
)
Iso
top
e
Irra
dia
tio
n t
arge
t H
alf
-lif
e
De
cay
pro
du
ct
Gam
ma
Co
nst
ant
Pro
du
ctio
n
Ro
ute
P
rob
ab
le
imp
uri
tie
s To
xici
ty
con
cern
s Sh
ipp
ing
Cla
ssif
icat
ion
Silic
on
-31
(S
i-31
) Si
lico
n d
ioxi
de,
SiO
2 1
57 m
in
P-3
1
0.0
00
30Si
(n,γ
)31Si
M
g-2
7, <
1%
N
W
hite
I
Po
tass
ium
-42
(K
-42
) P
ota
ssiu
m n
itra
te, K
NO
3
12.
4 h
C
a-4
2
0.1
37
41 K
(n,γ
)42 K
C
l-3
6, <
0.0
1%
N
Ye
llow
II
Sca
nd
ium
-46
(S
c-46
) Sc
and
ium
oxi
de,
Sc 2
O3
84
d
Ti-4
6
1.0
84
45Sc
(n,γ
)46Sc
N
/A
N
Yello
w II
I
Ch
rom
ium
-51
(C
r-51
) C
hro
miu
m (
III)
oxi
de,
C
r 2O
3
27.
7 d
V
-51
0.
018
50
Cr(
n,γ
)51C
r N
/A
N
Yello
w II
Zin
c-6
9m
(Zn
-69m
) D
eple
ted
Zin
c O
xid
e,
ZnO
(lo
w Z
n-6
4)
13.
9 h
Zn
-69,
G
a-6
9
0.2
40
68 Zn
(n,γ
)69
mZn
Zn
-65,
< 0
.1%
C
u-6
4, <
2%
C
u-6
7, <
0.2
%
N
Yello
w II
Ars
enic
-76
(A
s-7
6)
Ars
enic
(II
I) o
xid
e, A
s 2O
3
26.
4 h
Se
-76
0.
231
7
5 As(
n,γ
)76A
s N
/A
Y (≤
40
GB
q/g)
Ye
llow
II
Pal
lad
ium
-109
(P
d-1
09)
Palla
diu
m m
etal
, Pd
1
3.7
h
Ag-
109
0.
055
1
08P
d(n
,γ)1
09Pd
P
d-1
03, <
0.1
%
N
Yello
w II
An
tim
on
y-1
22
(Sb
-12
2)
An
tim
on
y (I
II)
oxi
de,
Sb
2O
3
2.7
2 d
Sn
-122
, Te
-12
2
0.2
57
121
Sb(n
,γ)1
22Sb
Sb
-124
, 2.5
%
N
Yello
w II
I
Bro
min
e-8
2
(Br-
82)
Am
mo
niu
m b
rom
ide,
N
H4B
r 3
5.3
h
Kr-
82
1.
450
81
Br(
n,γ)
82B
r B
r-8
0m, <
5 %
N
2
x Y
ello
w II
I
Ytt
riu
m-9
0
(Y-9
0)
Yttr
ium
oxi
de,
Y2O
3
64
h
Zr-9
0
0.0
00
89 Y(
n,γ
)90 Y
Y-
88,
~ 1
pp
m
N
Whi
te I
Sam
ariu
m-1
53
(Sm
-15
3)
Sam
ariu
m-1
52
oxi
de,
15
2Sm
2O3
47
h
Eu-1
53
0.0
49
152
Sm(n
,γ)1
53Sm
G
d-1
53, <
1%
Sm
-15
1<0
.01
%
N
Yello
w II
Euro
piu
m-1
52
(E
u-1
52
) Eu
ropi
um
oxi
de,
Eu
2O
3
12.
7 y
Gd
-152
, Sm
-15
2
0.6
44
151
Eu(n
,γ)1
52Eu
Eu
-154
, 6-7
%
N
Yello
w II
9
Terb
ium
-160
(T
b-1
60
) Te
rbiu
m o
xid
e, T
b2O
3
72
d
Dy-
160
0.
610
1
59Tb
(n,γ
)160
Tb
N/A
N
Ye
llow
II
Thu
liu
m-1
70
(Tm
-170
) Th
uliu
m o
xid
e, T
m2O
3 1
29 d
Er
-170
, Yb
-170
0.
002
1
69Tm
(n,γ
)170
Tm T
a-1
82, <
0.1
%
N
Whi
te I
Lute
tiu
m-1
77
(Lu
-17
7)
Lute
tium
-17
6
oxy
chlo
rid
e, 1
76Lu
OC
l 6
.7 d
H
f-1
77
0.0
20
176
Lu(n
,γ)1
77Lu
Lu
-177
m,
<0.0
1%
N
Whi
te I
Lute
tiu
m-1
77
(Lu
-17
7, n
.c.a
.)
Ytte
rbiu
m-1
76
oxi
de,
1
76Yb
2O3
6.7
d
Hf-
177
0.
020
1
76Yb
(n,γ
)177
Yb
→ 1
77Lu
N
/A
N
Whi
te I
Rh
en
ium
-18
6
(Re
-18
6)
Rh
eniu
m m
etal
or
amm
on
ium
pe
r-rh
enat
e
[NH
4][
ReO
4]
89
h
W-1
86,
Os-
186
0.
021
1
85R
e(n
,γ)1
86R
e
Re
-18
8, 0
.2-
2.5
%
N
Whi
te I
Rh
en
ium
-18
6
(Re
-18
6)
Rh
eniu
m-1
85
met
al,
185R
e (
99
% e
nri
ched
) 8
9 h
W
-186
, O
s-1
86
0.0
21
185
Re(
n,γ
)186
Re
R
e-1
88
, <0.
1%
N
W
hite
I
Rh
en
ium
-18
8
(Re
-18
8)
Rh
eniu
m-1
87
met
al,
187R
e (
99
% e
nri
ched
) 1
7 h
O
s-1
88
0.0
43
187
Re(
n,γ
)188
Re
R
e-1
86,
<5
%
N
Yello
w II
Tun
gste
n-1
87
(W-1
87)
Tu
ngs
ten
-18
6 (V
I) o
xid
e,
186
WO
3
24
h
Re
-18
7
0.4
24
186
W(n
,γ)1
87W
W
-185
, <0.
1%
N
Ye
llow
III
Irid
ium
-19
2
(Ir-
192)
Ir
idiu
m m
etal
7
4 d
O
s-1
92,
Pt-
192
0.
483
1
91Ir
(n,γ
)192
Ir
Ir-1
94, ~
0.5
%
N
Yello
w II
Irid
ium
-19
4
(Ir-
194)
Ir
idiu
m-1
93 m
etal
, 193
Ir
(99
% e
nri
ched
) 1
9 h
P
t-19
4
0.0
51
193
Ir(n
,γ)1
94Ir
Ir
-192
, ~0
.5%
Ir
-194
m,
~0.0
25%
N
Ye
llow
II
Go
ld-1
98
(A
u-1
98
) G
old
wir
e (A
u)
2.7
d
Hg-
198
0.
235
1
97A
u(n
,γ)1
98A
u
Au
-196
, <0.
1%
N
Ye
llow
II
10
Ta
ble
5. T
ier
3 r
adio
iso
top
es a
vaila
ble
fro
m M
NR
(1
GB
q)
Iso
top
e
Irra
dia
tio
n t
arge
t H
alf
-lif
e
De
cay
pro
du
ct
Gam
ma
Co
nst
an
t P
rod
uct
ion
Ro
ute
P
rob
ab
le
imp
uri
tie
s To
xici
ty
con
cern
s Sh
ipp
ing
Cla
ssif
icat
ion
Ph
osp
ho
rus-
32
(P-3
2)
Ma
gnes
ium
pyr
o-
ph
osp
hat
e, M
g 2P
2O
73
2 d
S-
32
0
.00
0
31 P(
n,γ
)32P
N
a-2
4, <
1%
N
W
hite
I/
Yello
w II
Ch
rom
ium
-51
(C
r-5
1)
Ch
rom
ium
-50
met
al
27.
7 d
V
-51
0
.01
8
50 C
r(n
,γ)51
Cr
N/A
N
Ye
llow
II
Co
ba
lt-6
0
(Co
-60
)
Co
bal
t m
eta
l or
cob
alt
(II)
oxi
de,
C
oO
5
.0 y
N
i-6
0 1
.29
1
59 C
o(n
,γ)60
Co
C
o-5
8, <
0.1
%
Fe-5
9, <
0.1
%
N
2 x
Yello
w II
I
Sele
niu
m-7
5 (S
e-7
5)
Sele
niu
m-7
4 m
etal
1
20 d
A
s-7
5 0
.63
6
74 Se
(n,γ
)75Se
A
s-7
4, <
1%
Y
(~1
00
GB
q/g
) Ye
llow
III
Ru
bid
ium
-86
(R
b-8
6)
Ru
bid
ium
ca
rbo
nat
e, R
b2C
O3
18.
6 d
Sr
-86,
Kr-
86
0.0
50
8
5 Rb
(n,γ
)86R
b
Rb
-84,
<0
.1%
N
Ye
llow
II
Rh
od
ium
-105
(R
h-1
05
) R
uth
en
ium
-10
4
met
al
35
h
Pd-1
05
0.0
44
1
04R
u(n
,γ)1
05R
u→
105
Rh
Ru
-105
t, <
1%
N
Ye
llow
II
Pal
lad
ium
-109
(P
d-1
09)
Palla
diu
m-1
08
met
al, 1
08Pd
1
3.7
h
Ag-
109
0
.05
5
108
Pd(n
,γ)10
9 Pd
N
N
Ye
llow
II
Silv
er-1
10m
(A
g-1
10m
) Si
lver
met
al (w
ire)
, A
g 2
50 d
C
d-1
11,
Ag-
110
1
.49
0
109
Ag(
n,γ
)110
mA
g
Ag-
108
, 0.0
1%
N
2
x Ye
llow
III
An
tim
on
y-1
22
(Sb
-12
2)
An
tim
on
y-12
1
oxi
de, 1
21Sb
2O
3 (9
9%
en
rich
ed)
2.7
2 d
Sn
-122
,
Te-1
22
0
.25
7
121
Sb(n
,γ)12
2Sb
Sb
-124
, <0.
1%
N
Ye
llow
III
Ce
siu
m-1
34
(C
s-1
34)
Ces
ium
car
bo
nat
e,
Cs 2
CO
3, o
r ce
siu
m
chlo
rid
e, C
sCl
2.0
6 y
B
a-1
34
0.8
79
1
33C
s(n
,γ)13
4C
s N
/A
N
Yello
w II
I
Ce
riu
m-1
43/
P
rasm
-143
(C
e-
143
/Pr-
143
)
Cer
ium
-142
(IV
) o
xid
e, 1
42C
eO
2 (
99
%
enri
ched
)
33
h
13.
6 d
Pr
-14
3,
Nd
-143
0
.18
1
0.0
00
1
42C
e(n
,γ)1
43C
e→
143
Pr
Ce
-14
1, <
0.1
%
N
Yello
w II
11
P
rom
eth
ium
-1
49 (
Pm
-149
) N
eod
ymiu
m-1
48
o
xid
e, 14
8 Nd
2O3
53.
1 h
Sm
-14
9
0.0
07
1
48N
d(n
,γ)1
49N
d→
14
9P
m
Pm
-14
7,
Pm
-15
1
N
Yello
w II
Euro
piu
m-1
52
(Eu
-15
2)
Euro
piu
m-1
51
oxi
de,
151
Eu2O
3
12.
7 y
G
d-1
52,
Sm-1
52
0
.64
4
151
Eu(n
,γ)15
2Eu
Eu
-154
, <0.
1%
N
Ye
llow
II
Gad
olin
ium
-1
59 (
Gd
-15
9)
Gad
olin
ium
-15
8 o
xid
e, 15
8 Gd
2O3
18.
6 h
Tb
-159
0
.03
4
158
Gd
(n,γ
)159G
d
N
N
Yello
w II
Dys
pro
siu
m-
165
/Ho
lmiu
m-
166
(D
y-1
65/
H
o-1
66)
Dys
pro
siu
m-1
64
oxi
de,
164
Dy 2
O3
81.
6 h
2
6.8
h
Ho
-16
6,
Er-1
66
0.0
16
0
.03
0
164
Dy(
n,γ
)165 D
y (n
,γ)16
6 Dy →
166
Ho
D
y-1
65, <
1%
N
Ye
llow
II
Ytt
erb
ium
-17
5 (Y
b-1
75
) Yt
terb
ium
-17
4
oxi
de,
174
Yb2O
3
4.2
d
Lu-1
75
0.0
23
1
74Yb
(n,γ
)175Yb
Yb
-169
, <0.
1%
N
Ye
llow
II
Tan
talu
m-1
82
(T
a-1
82
) Ta
nta
lum
(V
) o
xid
e,
Ta2O
5
114
d
W-1
82
0.6
88
1
81Ta
(n,γ
)182Ta
N
N
Ye
llow
III
Osm
ium
-18
5
(Os-
185
)
Osm
ium
-18
4 m
etal
, 1
84O
s (3
8+%
en
rich
ed)
93.
6 d
R
e-1
85
0
.48
9
184
Os(
n,γ
)185O
s O
s-1
89m
, tb
d
N
Yello
w II
I
Osm
ium
-19
1
(Os-
191
)
Osm
ium
-19
0 m
etal
, 1
90O
s (9
9%
enri
ched
) 1
5 d
Ir
-191
0
.20
7
190
Os(
n,γ
)191O
s O
s-1
91m
, 0
.5%
N
Ye
llow
II
Osm
ium
-19
1m
(O
s-19
1m
)
Osm
ium
-19
0 m
etal
, 1
90O
s (9
9%
enri
ched
) 1
3 h
O
s-1
91,
Ir-1
91
0.0
69
1
90O
s(n
,γ)1
91m
Os
Os-
191
, 6%
N
Ye
llow
II
Osm
ium
-19
3
(Os-
193
)
Osm
ium
-19
2 m
etal
, 1
92O
s (9
9%
enri
ched
) 3
1.5
h
Ir-1
93
0.0
74
1
92O
s(n
,γ)19
3O
s N
N
Ye
llow
II
Thal
liu
m-2
04
(T
l-20
4)
Thal
lium
ch
lori
de,
Tl
Cl
3.7
8 y
H
g-2
04,
Pb-2
04
0.0
03
2
03Tl
(n,γ
)204Tl
Tl
-202
, <1%
Y
(1 G
Bq
/g)
Whi
te I
12
Chromium-51, antimony-122, and europium-152 appears as both Tier 2 and Tier 3 radioisotopes. In the latter case, they are generated from isotopically enriched targets which greatly reduces the burden of radionuclidic impurities. Radioactive by-products in Sb-122, Pr-143, Pm-149, Eu-152, Yb-169 and Os-185/191/191m/193 are largely due to thermal neutron activation, and their proportion can be calculated in advance of the irradiation once the isotopic composition of the enriched target is known. Radioactive impurities in P-32 (Na-24), Rb-86 (Rb-84), and Tl-204 (Tl-202, (t½ = 12.2 d) are caused by fast neutron reactions and must be measured empirically; this has been done for thallium-202/204 in medium flux capsule sites (see Table 5).
Note that both osmium-191 (t½ = 15 d) and osmium-191m (t½ = 13 h) are produced from the same enriched target material (Os-190) using different irradiation and decay parameters. To generate the short-lived metastable isotope Os-191m, the time in-core is kept to a minimum and the sample is shipped as close to end of irradiation as possible; to favour the longer-lived Os-191, the activation time is increased to two operating days, and the sample stored underwater for 5 days prior to shipment.
Tier 4 radioisotopes (Table 6) are those which require an extended (> 1 operating week) period of time in-core, or a particularly expensive target material, or processing and handling time in the laboratory. Lead times for these isotopes are generally higher than for Tier 1-3 radioisotopes because of the extended irradiation times, and the need in nearly all cases for procurement of an isotopically enriched target.
Producing high purity radioisotopes of the lanthanoid elements (La, Pr-Lu) is particularly challenging because the chemical properties of these metals are so similar, and many of their stable isotopes have large neutron capture cross-sections. Even when ultrapure (> 99.99+%) lanthanoid oxide is procured, the presence of a trace amount of another lanthanoid at the parts per thousand or even parts per million level can result in significant radionuclidic impurities.
Additionally, processes used for stable isotope enrichment can lead to reduced chemical purity of the enriched isotope, as isobars with nearly identical chemical properties cannot be separated by centrifugation. An example of this is the samarium-152/gadolinium-152 pair: when the Gd-152 content of a gadolinium sample is enriched from an initial 0.2% to a maximal 30%, the isobar Sm-152 concentrates to multiple parts per thousand within the enriched isotope, resulting in increased isotopic purity, but decreased chemical purity. The same phenomenon occurs when enriching the Sm-152 content of stable samarium. Thus the production of Gd-153 or Sm-153 from an isotopically enriched target always produces a mixture of these two radioisotopes that can only be accurately predicted with access to a detailed Certificate of Analysis for the particular lot of enriched isotope. Concentration of Eu-151, Eu-153, and Gd-152 within similar-mass isotopes of other chemical elements is particularly problematic because of their abnormally large neutron capture cross-sections, and the long half-lives of the radioisotopes they form upon thermal neutron activation.
Radioisotopes categorized as Tier 5 (See Table 7) would require significant new infrastructure or research and development to be produced at the 1 GBq level. For example, McMaster University has previously developed a process for producing, separating, and purifying iodine-131 from tellurium oxide targets. However, to increase production beyond the currently permitted level (30-300 MBq), the process would have to be automated and relocated to a hot cell or similarly shielded environment with dedicated ventilation capacity. Similarly, staff at MNR routinely manipulate the gaseous radioisotope xenon-125 during production of iodine-125: the technology used to conduct this highly specialized work was designed and commercialized in-house at McMaster, and can readily be deployed to produce radioisotopes of other Noble Gases such as krypton. However, a dedicated gas handling station would have to be built and commissioned, and an environmental assessment would have to be conducted to determine the potential impact of releases from containment. Lead times would vary from radioisotope to radioisotope, but are generally on the order of several months or more.
13
Ta
ble
6. T
ier
4 r
adio
iso
top
es a
vaila
ble
fro
m M
NR
(1
GB
q)
Iso
top
e
Irra
dia
tio
n t
arge
t H
alf
-lif
e
De
cay
pro
du
ct
Gam
ma
Co
nst
ant
Pro
du
ctio
n
Ro
ute
R
ad
ion
ucl
ide
imp
uri
tie
s To
xici
ty
con
cern
s Sh
ipp
ing
Cla
ssif
icat
ion
Iro
n-5
9
(Fe
-59)
Ir
on
-58
met
al o
r o
xid
e,
58 Fe
or
58 Fe
2O
3
44.
5 d
C
o-5
9
0.6
20
58 Fe
(n,γ
)59Fe
Fe
-55,
<0
.1%
N
Ye
llow
III
Stro
nti
um
-85
(S
r-85
) St
ron
tiu
m-8
4 c
arb
o-
nate
, 84Sr
CO
3 (
79
%)
65
d
Rb
-85
0.
553
8
4 Sr(n
,γ)8
5Sr
N
N
Ye
llow
III
Mo
lyb
de
nu
m-
99/
Tech
net
ium
-9
9m (
Mo
-99
/Tc-
99m
)
Mo
lyb
den
um
-98
(VI)
o
xide
, 98 M
oO
3
66
h
Tc-9
9m
→
Tc-9
9
0.0
91
98 M
o(n
,γ)9
9 Mo
Zr
-95,
<0
.1%
Tc
-99
m, 1
00%
N
Ye
llow
II
Ru
then
ium
-10
3 (R
u-1
03
) R
uth
eniu
m-1
02
met
al,
102
Ru
3
9 d
R
h-1
03
0.2
87
102
Ru
(n,γ
)103
Ru
R
h-1
05, <
0.1
%
N
Yello
w II
Pal
lad
ium
-103
(P
d-1
02)
Palla
diu
m m
etal
, Pd
1
7 d
R
h-1
03(m
) 0.
130
1
02Pd
(n,γ
)103
Pd
N
N
Ye
llow
II
An
tim
on
y-1
24
(Sb
-12
4)
An
tim
on
y-12
3 o
xid
e,
123Sb
2O
3
60
d
Te-1
24
0.
958
1
23Sb
(n,γ
)124
Sb
N
N
Yello
w II
I
Euro
piu
m-1
54
(E
u-1
54
) Eu
ropi
um
-153
oxi
de,
15
3Eu
2O
3
8.5
y
Gd
-15
4,
Sm-1
54
0.
606
1
53Eu
(n,γ
)154
Eu
Eu-1
52, <
25%
N
Ye
llow
III
Gad
olin
ium
-153
(G
d-1
53
) G
ado
liniu
m-1
52
oxi
de
, 1
52G
d2O
3 (
30
%)
242
d
Eu-1
53
0.
084
1
52G
d(n
,γ)1
53G
d
Sm-1
53
, <1%
N
Ye
llow
II
Terb
ium
-161
(T
b-1
61
) G
ado
liniu
m-1
60
oxi
de
, 1
60G
d2O
3
6.9
d
Dy-
161
0.
049
1
60G
d(n
,γ)1
61G
d
→ 1
61Tb
Tb
-160
(tb
d)
N
Whi
te I
Ho
lmiu
m-1
66
(H
o-6
6, n
.c.a
.)
Dys
pro
siu
m-1
64
oxi
de,
1
64D
y 2O
3 (+
se
par
atio
n)
26.
8 h
Er
-16
6
0.0
16
164
Dy(
n,γ
)165
Dy
(n,γ
)166
Dy
→1
66H
o
N
N
Yello
w II
Erb
ium
-16
9
(Er-
169)
Er
biu
m-1
68
oxi
de
9
.4 d
Tm
-169
0.
000
1
68Er
(n,γ
)169
Er
Tm-1
71,
<0.0
5%
N
Whi
te I
14
Y
tte
rbiu
m-1
69
(Yb
-16
9)
Ytte
rbiu
m-1
68
oxi
de,
1
68Yb
2O
3 (
40
%)
32
d
Tm-1
69
0.1
93
168
Yb(n
,γ)1
69Yb
Yb
-175
(tb
d)
N
Yello
w II
Ha
fniu
m-1
81
(Hf-
181
) H
afn
ium
-180
oxi
de,
18
0H
fO2
42.
5 d
Ta
-18
1
0.3
07
180
Hf(
n,γ
)181
Hf
Hf-
179
m, <
1%
N
Yello
w II
Pro
tact
iniu
m-
233
(P
a-2
33)
Th
ori
um
oxy
-bis
-(n
itra
te),
Th
(O)(
NO
3) 2
2
7 d
U
-23
3
0.3
05
232
Th(n
,γ)2
33Th
→
233
Pa
N
N
Sa
fegu
ard
ed1
Tab
le 7
. Tie
r 5
rad
iois
oto
pes
ava
ilab
le f
rom
MN
R (
1 G
Bq
)
Iso
top
e
Irra
dia
tio
n t
arge
t H
alf
-lif
e
De
cay
pro
du
ct
Gam
ma
Co
nst
ant
Pro
du
ctio
n
Ro
ute
R
ad
ion
ucl
ide
imp
uri
tie
s To
xici
ty
con
cern
s Sh
ipp
ing
Cla
ssif
icat
ion
Ph
osp
ho
rus-
33
(P-3
3
Sulf
ur-
33,
33 S 8
(+
sep
ara
tio
n)
25
d
S-33
0.
000
33
S(n
,p)3
3 P
S-3
5 (t
bd
) N
W
hite
I
Kry
pto
n-7
9
(Kr-
79)
Kry
pto
n-7
8, 7
8 Kr
35
h
Br-
79
0.
443
7
8 Kr(
n,γ
)79 K
r T/
D
N
Yello
w II
I
Iod
ine
-131
(I
-13
1)
Tellu
riu
m o
xid
e, T
eO2
(+se
pa
rati
on
) 8
d
Xe
-13
1
0.2
20
130Te
(n,γ
) 1
31(m
) Te →
131
I N
/A
N
Yello
w II
Xe
no
n-1
27
(Xe
-12
7)
Xen
on
-126
, 1
26X
e
36.
4 d
I-
127
0.
216
1
26Xe
(n,γ
)127
Xe
T/
D
N
Yello
w II
Xe
no
n-1
33
(Xe
-13
3)
Xen
on
-132
, 1
32X
e
5.2
4 d
C
s-13
3
0.0
54
132
Xe(n
,γ)1
33X
e
T/D
N
Ye
llow
II
Xe
no
n-1
35
(Xe
-13
5)
Xen
on
-134
, 1
34X
e
9.1
h
Cs-
135
0.
139
1
34Xe
(n,γ
)135
Xe
T/
D
N
Yello
w II
1 N
ote
th
at
wh
ile p
rota
ctin
ium
-23
3 is
pro
du
ced
on
-dem
and
at
MN
R t
o s
up
po
rt n
ucl
ear
fore
nsi
cs, t
his
rad
iois
oto
pe
is s
ub
ject
to
nu
clea
r sa
fegu
ard
s, a
nd
can
o
nly
be
dis
trib
ute
d t
o si
tes
wit
h a
pp
rop
riat
e C
NSC
au
tho
riza
tio
n.
15
Finally, there is an additional group of radioisotopes that can be produced in limited quantities at MNR, but cannot be produced at the GBq level at a reasonable cost given the reactor’s current operating cycle. These isotopes include cobalt-58 (Co-58, t½ = 70.8 d), nickel-63 (Ni-63, t½ = 100 y), arsenic-77 (As-77, t½ = 39 h), krypton-85 (Kr-85, t½ = 10.8 y), strontium-89 (Sr-89, t½ = 50.5 d), cadmium-109 (Cd-109, t½ = 453 d), tin-117m (Sn-117m, t½ = 14 d), tellurium-123m (Te-123m, t½ = 120 d), cerium-141 (Ce-141, t½ = 32.5 d), and promethium-147 (Pm-147, t½ = 2.626 y). More detailed information on production routes, quantities available, and lead times can be obtained from McMaster upon request.
5. Radioisotope Production Capacity at MUCF
For the past 10 years, the McMaster University Cyclotron Facility (MUCF) has been used exclusively to produce fluorine-18 for clinical use. Large-scale production of this isotope was discontinued at the end of 2020, and the facility is being rededicated to supporting research through more diversified, smaller-scale radioisotope production. A short list of potential production candidates for has been created (see Table 8), and development work into targetry for the production of zirconium-89 and gallium-67 has begun.
Table 8. Radioisotope production candidates for MUCF
Isotope Production Route Half-life Decay product
Manganese-52 (Mn-52) 52Cr(p,n) 52Mn 5.6 d Cr-52
Copper-64 (Cu-64) 64Ni(p,n)64Cu 12.7 h Ni-64, Zn-64
Arsenic-74 (As-74) natGe(p,xn)74As 17.8 d Ge-74, Se-74
Bromine-76 (Br-76) 76Se(p,n)76Br 16 h Se-76
Gallium-67 (Ga-67) 67Zn(p,n)67Ga 3.26 d Zn-67
Gallium-68 (Ga-68) 68Zn(p,n)68Ga 68 min Zn-68
Germanium-69 (Ge-69) 69Ga(p,n)69Ge 39 h Ga-69
Indium-111 (In-111) 111Cd(p,n)111In 2.8 d Cd-111
Iodine-124 (I-124) 124Te(p,n)124I 4.2 d Te-124
Palladium-103 (Pd-103) 103Rh(p,n)103Pd 17 d Rh-103
Technetium-99m (Tc-99m) 100Mo(p,n)99mTc 6.0 h Tc-99→Ru-99
Yttrium-86 (Y-86) 86Sr(p,n)86Y 14.7 h Sr-86
Zirconium-89 (Zr-89) 89Y(p,n)89Zr 78 h Y-89
Based on data available in the scientific literature, research staff at McMaster are confident that the radioisotopes in Table 8 can be prepared at the 1 GBq level. However, the precise quantities and radionuclidic purity of these isotopes cannot be determined without additional experimental work. Cyclotron-based radioisotope production is significantly more challenging to model from first principles compared to the reactor-based approach. For example, in reactor-based production, the amount of
16
radioisotope produced scales linearly with target mass, and can be calculated from the standard yield equation. This is possible because the sample is thoroughly immersed in a neutron field during irradiation, and the highly penetrating neutrons experience minimal attenuation when passing through thick targets of most materials. However, in cyclotron-based radioisotope production, a beam of protons is used to bombardment the target: this beam has a finite size and minimal penetrating power. Thus increasing the surface area or the volume of a solid target does not induce a proportionate increase in amount of radioisotope produced.
Another key difference is the maximum particle flux to which the irradiation target can be exposed. New targets for reactor-based radioisotope production can be inserted directly into the reactor core at standard operating power as long as the material has a melting point in excess of 300 °C and an appropriate cross-section. The neutron flux and maximum irradiation duration are therefore determined by the site characteristics and operating cycle of the nuclear reactor, and are not limited by the target itself. In contrast, in a cyclotron, the maximum beam current and irradiation time that a given target can withstand must be determined empirically through a series of low-intensity proton bombardment experiments. As the beam current and irradiation duration are slowly increased, the impact of beam heating on target integrity is closely monitored to identify the envelope of viable operating conditions for that particular target. Because each irradiation target has different thermal properties (melting point, heat transfer, cooling capacity), it will also have a unique tolerance of both beam current and duration of bombardment. As beam current corresponds to particle flux, this means that two different targets cannot necessarily be exposed to the same particle flux inside the same cyclotron – and the majority of targets cannot withstand the intensity of the instrument’s full-strength proton beam.
As proton bombardment typically induces a wider range of nuclear reactions compared to neutron bombardment, the radionuclidic impurities within a given target post-bombardment cannot necessarily be predicted accurately. Once the maximum beam current and irradiation duration have been determined experimentally, incidental activation products will be identified and quantified by gamma spectroscopy. Radioactive by-products are expected to necessitate chemical processing and purification of all radioisotopes produced at MUCF; thus, these radioisotopes will always be supplied as solutions, not solids.
The first step toward assessing production capacity for a given radioisotope at MUCF is thus to design, model, and fabricate an irradiation target and complete the necessary licensing application to begin a series of low-intensity proton bombardments. This is followed by by-product evaluation assessment, development and validation of a purification strategy, and securing additional licensing to enable scale-up of the radioisotope processing. The development of production capacity for a particular cyclotron-generated radioisotope thus requires significant human and material resources, and involved timelines on the order of months. This work is currently in progress for zirconium-89, with additional work planned for gallium-67 later in 2021. By the end of 2021, MUCF is expected to begin producing MBq of zirconium-89 (as an oxalate solution) to complement weekly production of fluorine-18. The choice of which radioisotopes to pursue subsequently will be influenced by researcher demand and commercial factors.
6. Summary & Conclusion
The McMaster Nuclear Reactor is capable of producing dozens of different radioisotopes at the 1 GBq level with lead times on the order of days to months. The cost of each radioisotope will depend on the precise conditions used to generate it. These primarily neutron-rich radioisotopes are complemented by the production capabilities of the McMaster University Cyclotron Facility, which can generate an additional dozen neutron-deficient radioisotopes. Efforts have begun to realize the full potential of the MUCF, with new radioisotopes expected in routine production by the end of 2021.
DOCUMENT CONTROL DATA *Security markings for the title, authors, abstract and keywords must be entered when the document is sensitive
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Radioisotope Production Capabilities at McMaster University
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Armstrong, A.
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February 2021
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Radiation; Nuclear; Procurement
13. ABSTRACT/RÉSUMÉ (When available in the document, the French version of the abstract must be included here.)
McMaster University is a world leader in radioisotope production. It is the only site in Canada that can make both cyclotron-and nuclear reactor-generated radioisotopes. Nearly 100 different radioisotopes can be generated at McMaster University, with lead times ranging from 1–2 weeks to several months. The cost and purity of each radioisotope depends on the precise conditions used to generate it.
L’Université McMaster est un leader mondial de la production de radio-isotopes. C’est le seul site au Canada qui peut produire à la fois des radio-isotopes générés par des cyclotron et des réacteurs nucléaires. Près de 100 radio-isotopes différents peuvent être produits à l’Université McMaster, avec des délais allant de 1 à 2 semaines à plusieurs mois. Le coût et la pureté de chaque radio-isotope dépendentdes conditions précises utilisées pour la générer.