Supplementary data
Journal title: Journal of Radioanalytical and Nuclear Chemistry
Article Title: Reactor production of 32P for medical applications: A comparative
assessment of 32S(n,p)32P and 31P(n,)32P methods
K.V. Vimalnath, Priyalata Shetty, A. Rajeswari, Viju Chirayil,
Sudipta Chakraborty, Ashutosh Dash*
Isotope Applications & Radiopharmaceuticals Division,
Bhabha Atomic Research Centre,
Trombay, Mumbai, India 400 085.
*Corresponding Author: adash@barc.gov.in
Materials and Methods
Irradiated target processing facility
Processing of the neutron irradiated target was carried out in a leak tight isotope
processing facility consisting of stainless steel boxes [ 1.8 ×1.8 × 0.9 m3] with 100 mm lead
shielding wall all-around and equipped with remote handling tongs, lead viewing windows and
other associated remote accessories. Movement of material and equipment throughout the facility
was carried out by an electric motor powered trolley mounted on stainless steel rail. The trolley
runs through the entire length of the box and ends at a tunnel. In order to simplify operation in a
remotely operated shielded facility, gadgets such as irradiation can cutting unit, remote vial
crimping and decrimping etc. were specially made and installed inside the shielded facility.
Equipments inside the cell were manipulated with remote handling tongs. All operations were
performed according to prescribed radioactive work procedure in a shielded facility.
All processing equipments including quartz distillation assembly for the distillation of
neutron irradiated sulfur, receiver, ion exchange column, evaporating flask and storage container,
were designed and fabricated in house and installed inside the shielded facility.
Experimental
Radiological safety
In view of radioactive nature of
32
P safe and approved radioactive procedures were
adopted during the irradiated target processing procedures. All the plant operations were carried
out after thorough planning in order to achieve ‘ALARA’. The personnel involved in this work
were monitored for radiation exposure levels by TLD dosimeters. Continuous air sampling of
work area was performed to monitor levels of airborne radioactivity and to maintain safe levels
of radiological safety.
Results
32S(n,p)32P
production process
Target
Natural S atom consists of 32S (95.02%), 33S (0.75%), 34S (4.21%) and 36S (0.02%). When
sulfur undergoes irradiation in a reactor, it is imperative to consider all the radionuclides
produced both by thermal and fast neutrons. Table S1 depicts the nuclear reactions taking place
when natural sulfur undergoes irradiation with thermal and fast neutrons in a nuclear reactor. It is
seen from the Table. S1 that among all the possible radionuclides formed by natural S neutron
irradiation, only
35
S (T1/2 = 87.2 d) and
33
P (T1/2 = 25.3 d) are of concern and could be
radiochemical impurities of the final product 32P (T1/2 = 14.28 d). Concern due to 35S is least as it
will remain with cold S during chemical separation. The contribution 33P is a point of concern as
it is neither possible to separate nor feasible to reduce by cooling owing to its longer half life
than
32
P. Experimentally it was observed that the ratio between the
32
P and
33
P activities
produced in the same irradiation conditions is about 7000, because the much lower isotopic
abundance and poor fast neutron cross section of 33S target as well as longer half life of 33P.
Processing of neutron irradiated sulfur
In view of the need to isolate
32
P formed during the neutron irradiation of target,
radiochemical processing of irradiated sulfur target is necessary and a wide range of wet
chemical extraction process such as liquid-liquid extraction technique, precipitation and dry
distillation methods have been successfully used [1]. The wet extraction method consists of
dissolution of irradiated powdered sulfur in boiling water in the presence of strong and weak
acids to extract the phosphorus nuclide from the sulfur target using 2-octanol [2,3]. One of the
major impediments of this wet chemical extraction method is the dependence of extraction yield
with the particle size of the irradiated sulfur target and is significantly decreased when the target
is melted or solidified due to the exothermal heat during neutron irradiation. Additionally, the
use of mineral acid is a major deterrent as it induces impurities and leaves solid waste behind,
which not only complicates the extraction but also requires additional purification step to achieve
required purity. The requirement of multi-stage processes results in poor recovery yields. Owing
to these drawbacks, assessing the potential of dry distillation technique in not only an interesting
prospect, but viewed as a necessity.
(n, ) 32P method of production
In light of the perceived need to obtain 32P having desirable specific activity and yield, a
thorough and systematic optimization of irradiation parameters and radiochemical procedures
was consider worthwhile investigating.
Target
Stable phosphorus is mononuclidic
31
P (abundance: 100%), there is no direct competing
reactions due to other isotopes of phosphorus. While the use of elemental phosphorus in (n,γ) 32P
production method is the obvious choice in terms of productivity and simplicity in target
processing, selection of the allotropic form of P constitute one of the most important criterion as
it has three main allotropes including white, red and black and each one of them exhibit different
properties. The option of using white phosphorus is precluded as it is toxic, volatile (melting
point 44.2oC), thermodynamically unstable and can spontaneously ignite when it comes in
contact with air. In this context, the scope of using red phosphorus seems to be the ideal choice
as it is far more stable than the white allotrope and does not catch fire in air at temperatures
below 240°C.Red phosphorus is formed after heating white phosphorus to 250°C (482°F) or by
exposing white phosphorus to sunlight.
Neutron Irradiation
Nuclear reaction leading to production of 32P by radiative neutron capture is
 = 172 mb
31
P(n,) 32P
The yield and specific activity of
32
P produced via (n,γ) route of production is mostly
governed by the neutron flux and irradiation time. The variation of specific activity of
32
P
produced at the end of neutron irradiation as a function of irradiation time at different thermal
neutron fluxes has been calculated and the results are shown in Fig. S1. It is evident from the
Fig. S1 that higher the thermal neutron flux of the reactor, shorter will be the time of irradiation
for attaining the required specific activity. Although, the specific activity of
32
P produced at
higher duration of irradiation at a given thermal neutron flux is significantly high, due to reasons
concerning availability of neutron flux in Dhruva research reactor of our institute, irradiation at
neutron flux higher than 7.5×1013 n.cm-2.s-1 could not be availed. Therefore our subsequent
efforts were confined to this flux for production of
32
P. The
32
P activity produced at end of
neutron irradiation as a function of irradiation time at flux of 7.5×1013 n.cm-2.s-1 available in
Dhruva research reactor has been calculated and the results are shown in Fig S2. As evident from
Fig S2, specific activity of
32
P increases exponentially with increasing irradiation time and
reaches a value of 6.6 mCi 32P per mg P on 60th day of irradiation. Increase in specific activity
of 32P is marginal beyond 60 days of irradiation. Irradiation time upto 4 half life of 32P was thus
chosen to achieve practically maximum specific activity for subsequent studies and production.
Chemical processing
The choice of an appropriate reagent to dissolve neutron irradiated red phosphorous
target is a critical issue. The use of nonoxidizing acids such as hydrochloric acid was found to be
futile as it does not cause oxidation of red phosphorous. It transpires that oxidising acids are best
suited for this applications, and conc. HNO3 seems to be the obvious choice. The most striking
feature of HNO3 is its ability to dissolve red phosphorous and ease of use. About 9 mL conc.
HNO3 was found to effective for the dissolution of 350 mg of red phosphorus by gentle heating.
Quality control of 32P
Specific activity
Colorimetric method was used for determination of total PO43- content of the obtained 32P
solution in the radioactive solution owing to the absence of interfering ions such as Fe, Al etc in
the final product. Concentration of P was calculated making use of calibration curve constructed
using measurements of absorbance of solutions having known concentration of PO43- ions.
Radionuclidic (RN) purity
Table S2 depicts the nuclear reactions taking place in a nuclear reactor during irradiation
that leads to the concomitant formation of radionuclide impurities. The impurities of
76
As,122Sb,124Sb possibly arising from the presence of trace concentration of As and Sb in P
target due to their identical chemistry with P. Experimentally it was observed that co-produced
radionuclide impurities were present to the extent of 0.3 µCi 76As, 0.03 µCi 122Sb, 0.01 µCi 124Sb
per mCi of
32
P at end of irradiation, which works out to a radionuclide impurity content of
0.034%.
Radiochemical (RC) purity
Radiochemical purity determination is an important parameter to ascertain that product
radiochemical has
32
P as phosphate ion, which is the desirable form. Radiochemical purity is
important in radiopharmacy since it is the radiochemical form which determines the
biodistribution of the radiopharmaceutical. Radiochemical impurities will have different patterns
of biodistribution which may irradiate the non-targeted organ and render the therapy
meaningless. The radiochemical purities of typical batches of 32P obtained from 32S(n,p)32P and
(n,) 32P routes of production as determined by paper chromatography are shown in Fig S3 (a)
and (b) which indicate >98% of 32P as orthophosphate ion.
Figure captions
Fig. S1. Specific activity of
32
P produced at the end of neutron irradiation as a function of
irradiation time at different thermal neutron fluxes during the neutron irradiation of red
P.
Fig S2.
Specific activity of
32
P produced at the end of neutron irradiation as a function of
irradiation time at thermal neutron flux of 7.5 ×1013 n.cm-2.s-1.
Fig. S3.
Paper chromatographic pattern of 32P in isopropyl alcohol, water, 50% trichloroacetic
acid and 25% NH4OH solvent system (a) 32S(n,p)32P route and (b) 31P(n,γ)32P route
Table S1. Radionuclide production by natural sulfur irradiation with thermal and fast
neutrons
Isotope of S
Isotopic
abundance
(%)
Activation products formed
Fast neutrons irradiation
Nuclear
Half Life
Reaction
Thermal neutrons irradiation
Nuclear
Half Life
Reaction
32
95.02
32
14.26 d
32
Stable
33
0.75
33
25.3 d
33
Stable
34
4.21
34
14.4 s
34
87.2 d
36
0.02
36
5.9 s
36
5.05 m
S
S
S
S
S(n,p)32P
S(n,p)33P
S(n,p)34P
S(n,p)36P
S(n,)33S
S(n,)34S
S(n,)35S
S(n,)37S
Table S2. Production of radionuclide impurities during the neutron irradiation of red
phosphorous
Radionuclide
76
As
122
124
Sb
Sb
T1/2
1.09 d
2.7 d
60.2 d
Eβmax energy
used for
assay
keV
%
-
-
-
-
-
-
γ peaks used
for assay
Method of formation of the
radionuclides
keV
%
Nuclear
reaction
559.1
45
75
657.1
6.2
564
70
692.9
3.82
602.7
97.8
722.8
10.9
% natural
abundance
As(n,γ)
100
Reaction
cross
section
4.5 b
121
Sb(n,γ)
57.21
5.9 b
123
Sb(n,γ)
42.79
4.1 b
Specific Actiivty
32
P (mCi/mg)
8
7
13
 = 7.5x10
th
6
13
5
 = 5.5x10
4
 = 4.5x10
3
 = 3.5x10
th
13
th
13
th
13
 = 2.5x10
2
th
13
 = 1.5x10
th
1
0
0
20
40
60
80
100
120
Irradiation time (days)
Fig. S1. Specific activity of
32
P produced at the end of neutron irradiation as a function of
irradiation time at different thermal neutron fluxes during the neutron irradiation of red
P.
32P Specific Activity build up (mCi/mg)
8
6
4
2
0
20
40
60
80
100
120
Irradiation time (days)
Fig S2.
Specific activity of
32
P produced at the end of neutron irradiation as a function of
irradiation time at thermal neutron flux of 7.5 ×1013 n.cm-2.s-1.
30000
25000
Activity (cps)
20000
3PO4
15000
10000
5000
4P2O7
polyphosphate
0
0
5
10
15
20
25
30
Migration from the point of spotting (Cm)
(a)
40000
35000
PO4
Activity (cps)
30000
3-
25000
20000
15000
10000
5000
P 2O 7
polyphosphate
4-
0
0
5
10
15
20
25
Migration from the point of spotting (Cm)
30
(b)
Fig. S3.
Paper chromatographic pattern of 32P in isopropyl alcohol, water, 50% trichloroacetic
acid and 25% NH4OH solvent system (a) 32S(n,p)32P route and (b) 31P(n,γ)32P route
References
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Han HS , Park UJ, Shin HY, Yoo KM., (2007) Method for distillation of sulfur for the
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2.
Samsah
K, (1958) The Jener method for the extraction of pure
32
P from neutron-
irradiated sulfur. Atompraxis. 4 (14): 14-17.
3.
Razbash AA, Nerozin NA,
Panarin
MV, Sevast'yanov YG,
Polyakov ON,
Podsoblyaev DV, Smetanin EY, Dubinkina TA, Nikulin MP.( 1991). Winning 32P in
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